Apoptosis

, Volume 8, Issue 5, pp 413–450 | Cite as

Microtubules, microtubule-interfering agents and apoptosis

  • F. Mollinedo
  • C. Gajate
Article

Abstract

Microtubules are dynamic polymers that play crucial roles in a large number of cellular functions. Their pivotal role in mitosis makes them a target for the development of anticancer drugs. Microtubule-damaging agents suppress microtubule dynamics, leading to disruption of the mitotic spindle in dividing cells, cell cycle arrest at M phase, and late apoptosis. A better understanding of the processes coupling microtubule damage to the onset of apoptosis will reveal sites of potential intervention in cancer chemotherapy. Inhibition of microtubule dynamics induces persistent modification of biological processes (M arrest) and signaling pathways (mitotic spindle assembly checkpoint activation, Bcl-2 phosphorylation, c-Jun NH2-terminal kinase activation), which ultimately lead to apoptosis through the accumulation of signals that finally reach the threshold for the onset of apoptosis or through diminishing the threshold for engagement of cell death. Microtubules serve also as scaffolds for signaling molecules that regulate apoptosis, such as Bim and survivin, and their release from microtubules affect the activities of these apoptosis regulators. Thus, sustained modification of signaling routes and changes in the scaffolding properties of microtubules seem to constitute two major processes in the apoptotic response induced by microtubule-interfering agents.

apoptosis cancer chemotherapy microtubules microtubule-interfering agent mitotic spindle signal transduction 

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References

  1. 1.
    Fuchs E, Yang Y. Crossroads on cytoskeletal highways. Cell 1999; 98: 547-550.Google Scholar
  2. 2.
    Ruhrberg C, Watt FM. The plakin family: Versatile organizers of cytoskeletal architecture. Curr Opin Genet Dev 1997; 7: 392-397.Google Scholar
  3. 3.
    Leung CL, Liem RK, Parry DA, Green KJ. The plakin family. J Cell Sci 2001; 114: 3409-3410.Google Scholar
  4. 4.
    Leung CL, Green KJ, Liem RK. Plakins: A family of versatile cytolinker proteins. Trends Cell Biol 2002; 12: 37-45.Google Scholar
  5. 5.
    Lewis SA, Gilmartin ME, Hall JL, Cowan NJ. Three expressed sequences within the human beta-tubulin multigene family each define a distinct isotype. J Mol Biol 1985; 182: 11-20.Google Scholar
  6. 6.
    Villasante A, Wang D, Dobner P, et al. Six mouse alphatubulin mRNAs encode five distinct isotypes: Testis-specific expression of two sister genes. Mol Cell Biol 1986; 6: 2409-2419.Google Scholar
  7. 7.
    Laing N, Dahllof B, Hartley-Asp B, Ranganathan S, Tew KD. Interaction of estramustine with tubulin isotypes. Biochemistry 1997; 36: 871-878.Google Scholar
  8. 8.
    Pape M, Schnieder T, von Samson-Himmelstjerna G. Investigation of diversity and isotypes of the beta-tubulin cDNA in several small strongyle (Cyathostominae) species. J Parasitol 2002; 88: 673-677.Google Scholar
  9. 9.
    Woo K, Jensen-Smith HC, Luduena RF, Hallworth R. Differential synthesis of beta-tubulin isotypes in gerbil nasal epithelia. Cell Tissue Res 2002; 309: 331-335.Google Scholar
  10. 10.
    Arai K, Shibutani M, Matsuda H. Distribution of the class II beta-tubulin in developmental and adult rat tissues. Cell Motil Cytoskeleton 2002; 52: 174-182.Google Scholar
  11. 11.
    Banerjee A. Increased levels of tyrosinated alpha-, beta(III)-, and beta(IV)-tubulin isotypes in paclitaxel-resistant MCF-7 breast cancer cells. Biochem Biophys Res Commun 2002; 293: 598-601.Google Scholar
  12. 12.
    Walss-Bass C, Xu K, David S, Fellous A, Luduena RF. Occurrence of nuclear beta(II)-tubulin in cultured cells. Cell Tissue Res 2002; 308: 215-223.Google Scholar
  13. 13.
    McKean PG, Vaughan S, Gull K. The extended tubulin superfamily. J Cell Sci 2001; 114: 2723-2733.Google Scholar
  14. 14.
    Nicoletti MI, Valoti G, Giannakakou P, et al. Expression of beta-tubulin isotypes in human ovarian carcinoma xenografts and in a sub-panel of human cancer cell lines from the NCIAnticancer Drug Screen: Correlation with sensitivity to microtubule active agents. Clin Cancer Res 2001; 7: 2912-2922.Google Scholar
  15. 15.
    Burkhart CA, Kavallaris M, Band Horwitz S. The role of betatubulin isotypes in resistance to antimitotic drugs. Biochim Biophys Acta 2001; 2: O1-O9.Google Scholar
  16. 16.
    Hallworth R, Luduena RF. Differential expression of beta tubulin isotypes in the adult gerbil cochlea. Hear Res 2000; 148: 161-172.Google Scholar
  17. 17.
    Khan IA, Tomita I, Mizuhashi F, Luduena RF. Differential interaction of tubulin isotypes with the antimitotic compound IKP-104. Biochemistry 2000; 39: 9001-9009.Google Scholar
  18. 18.
    Walker RA, O'Brien ET, Pryer NK, et al. Dynamic instability of individual microtubules analyzed by video light microscopy: Rate constants and transition frequencies. J Cell Biol 1988; 107: 1437-1448.Google Scholar
  19. 19.
    Bailly E, Bornens M. Cell biology. Centrosome and cell division. Nature 1992; 355: 300-301.Google Scholar
  20. 20.
    Moudjou M, Bordes N, Paintrand M, Bornens M. gamma-Tubulin in mammalian cells: The centrosomal and the cytosolic forms. J Cell Sci 1996; 109: 875-887.Google Scholar
  21. 21.
    Moritz M, Braunfeld MB, Guenebaut V, Heuser J, Agard DA. Structure of the gamma-tubulin ring complex: A Microtubules and apoptosis template for microtubule nucleation. Nat Cell Biol 2000; 2: 365-370.Google Scholar
  22. 22.
    Oakley BR. Cell biology.Anice ring to the centrosome. Nature 1995; 378: 555-556.Google Scholar
  23. 23.
    Schnackenberg BJ, Khodjakov A, Rieder CL, Palazzo RE. The disassembly and reassembly of functional centrosomes in vitro. Proc Natl Acad Sci USA 1998; 95: 9295-9300.Google Scholar
  24. 24.
    Mitchison T, Kirschner M. Dynamic instability of microtubule growth. Nature 1984; 312: 237-242.Google Scholar
  25. 25.
    Cassimeris LU, Walker RA, Pryer NK, Salmon ED. Dynamic instability of microtubules. Bioessays 1987; 7: 149-154.Google Scholar
  26. 26.
    Cassimeris L, Pryer NK, Salmon6ED. Real-time observations of microtubule dynamic instability in living cells. J Cell Biol 1988; 107: 2223-2231.Google Scholar
  27. 27.
    Walker RA, Pryer NK, Salmon ED. Dilution of individual microtubules observed in real time in vitro: Evidence that cap size is small and independent of elongation rate. J Cell Biol 1991; 114: 73-81.Google Scholar
  28. 28.
    Mandelkow EM, Mandelkow E, Milligan RA. Microtubule dynamics and microtubule caps: A time-resolved cryoelectron microscopy study. J Cell Biol 1991; 114: 977-991.Google Scholar
  29. 29.
    Drechsel DN, Hyman AA, Cobb MH, Kirschner MW. Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau. Mol Biol Cell 1992; 3: 1141-1154.Google Scholar
  30. 30.
    Erickson HP, O'Brien ET. Microtubule dynamic instability and GTP hydrolysis. Annu Rev Biophys Biomol Struct 1992; 21: 145-166.Google Scholar
  31. 31.
    Hyman AA, Karsenti E. Morphogenetic properties of microtubules and mitotic spindle assembly. Cell 1996; 84: 401-410.Google Scholar
  32. 32.
    Andersen SS. Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends Cell Biol 2000; 10: 261-267.Google Scholar
  33. 33.
    Mandelkow E, Mandelkow EM. Microtubules and microtubule-associated proteins. Curr Opin Cell Biol 1995; 7: 72-81.Google Scholar
  34. 34.
    Masson D, Kreis TE. Binding of E-MAP-115 to microtubules is regulated by cell cycle-dependent phosphorylation. J Cell Biol 1995; 131: 1015-1024.Google Scholar
  35. 35.
    Ookata K, Hisanaga S, Sugita M, et al. MAP4 is the in vivo substrate for CDC2 kinase in HeLa cells: Identification of an M-phase specific and a cell cycle-independent phosphorylation site in MAP4. Biochemistry 1997; 36: 15873-15883.Google Scholar
  36. 36.
    Ookata K, Hisanaga S, Bulinski JC, et al. Cyclin B interaction with microtubule-associated protein 4 (MAP4) targets p34cdc2 kinase to microtubules and is a potential regulator of M-phase microtubule dynamics. J Cell Biol 1995; 128: 849-862.Google Scholar
  37. 37.
    Larsson N, Marklund U, Gradin HM, Brattsand G, Gullberg M. Control of microtubule dynamics by oncoprotein 18: Dissection of the regulatory role of multisite phosphorylation during mitosis. Mol Cell Biol 1997; 17: 5530-5539.Google Scholar
  38. 38.
    McNally FJ, Vale RD. Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 1993; 75: 419-429.Google Scholar
  39. 39.
    Ahmad FJ, Yu W, McNally FJ, Baas PW. An essential role for katanin in severing microtubules in the neuron. J Cell Biol 1999; 145: 305-315.Google Scholar
  40. 40.
    Belmont L, Mitchison T, Deacon HW. Catastrophic revelations about Op18/stathmin. Trends Biochem Sci 1996; 21: 197-198.Google Scholar
  41. 41.
    Belmont LD, Mitchison TJ. Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules. Cell 1996; 84: 623-631.Google Scholar
  42. 42.
    Marklund U, Osterman O, Melander H, Bergh A, Gullberg M. The phenotype of a “Cdc2 kinase target site-deficient” mutant of oncoprotein 18 reveals a role of this protein in cell cycle control. J Biol Chem 1994; 269: 30626-30635.Google Scholar
  43. 43.
    Marklund U, Larsson N, Brattsand G, et al. Serine 16 of oncoprotein 18 is a major cytosolic target for the Ca2+/calmodulin-dependent kinase-Gr. Eur J Biochem 1994; 225: 53-60.Google Scholar
  44. 44.
    Walczak CE, Mitchison TJ, Desai A. XKCM1: A Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly. Cell 1996; 84: 37-47.Google Scholar
  45. 45.
    Mandelkow E, Hoenger A. Structures of kinesin and kinesinmicrotubule interactions. Curr Opin Cell Biol 1999; 11: 34-44.Google Scholar
  46. 46.
    Xu Y, Takeda S, Nakata T, et al. Role of KIFC3 motor protein in Golgi positioning and integration. J Cell Biol 2002; 158: 293-303.Google Scholar
  47. 47.
    Noda Y, Okada Y, Saito N, et al. KIFC3, a microtubule minus end-directed motor for the apical transport of annexin XIIIbassociated Triton-insoluble membranes. J Cell Biol 2001; 155: 77-88.Google Scholar
  48. 48.
    Sorger PK, Dobles M, Tournebize R, Hyman AA. Coupling cell division and cell death to microtubule dynamics. Curr Opin Cell Biol 1997; 9: 807-814.Google Scholar
  49. 49.
    Oliferenko S, Balasubramanian MK. Astral microtubules monitor metaphase spindle alignment in fission yeast. Nat Cell Biol 2002; 4: 816-820.Google Scholar
  50. 50.
    Wheatley SP, Wang Y. Midzone microtubule bundles are continuously required for cytokinesis in cultured epithelial cells. J Cell Biol 1996; 135: 981-989.Google Scholar
  51. 51.
    Straight AF, Field CM. Microtubules, membranes and cytokinesis. Curr Biol 2000; 10: R760-R770.Google Scholar
  52. 52.
    Rudner AD, Murray AW. The spindle assembly checkpoint. Curr Opin Cell Biol 1996; 8: 773-780.Google Scholar
  53. 53.
    Li Y, Benezra R. Identification of a human mitotic checkpoint gene: hsMAD2. Science 1996; 274: 246-248.Google Scholar
  54. 54.
    Li X, Nicklas RB. Mitotic forces control a cell-cycle checkpoint. Nature 1995; 373: 630-632.Google Scholar
  55. 55.
    Zhou J, Yao J, Joshi HC. Attachment and tension in the spindle assembly checkpoint. J Cell Sci 2002; 115: 3547-3555.Google Scholar
  56. 56.
    Ru HY, Chen RL, Lu WC, Chen JH. hBUB1 defects in leukemia and lymphoma cells. Oncogene 2002; 21: 4673-4679.Google Scholar
  57. 57.
    Skoufias DA, Andreassen PR, Lacroix FB, Wilson L, Margolis RL. Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints. Proc Natl Acad Sci USA 2001; 98: 4492-4497.Google Scholar
  58. 58.
    Brady DM, Hardwick KG. Complex formation between Mad1p, Bub1p and Bub3p is crucial for spindle checkpoint function. Curr Biol 2000; 10: 675-678.Google Scholar
  59. 59.
    Li Y, Gorbea C, Mahaffey D, Rechsteiner M, Benezra R. MAD2 associates with the cyclosome/anaphase-promoting complex and inhibits its activity. Proc Natl Acad Sci USA 1997; 94: 12431-12436.Google Scholar
  60. 60.
    Dobles M, Liberal V, Scott ML, Benezra R, Sorger PK. Chromosome missegregation and apoptosis in mice lacking the mitotic checkpoint protein Mad2. Cell 2000; 101: 635-645.Google Scholar
  61. 61.
    Fang G. Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex. Mol Biol Cell 2002; 13: 755-766.Google Scholar
  62. 62.
    Taylor SS, McKeon F. Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell 1997; 89: 727-735.Google Scholar
  63. 63.
    Taylor SS, Ha E, McKeon F. The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase. J Cell Biol 1998; 142: 1-11.Google Scholar
  64. 64.
    Cahill DP, Lengauer C, Yu J, et al. Mutations of mitotic checkpoint genes in human cancers. Nature 1998; 392: 300-303.Google Scholar
  65. 65.
    Martinez-Exposito MJ, Kaplan KB, Copeland J, Sorger PK. Retention of the BUB3 checkpoint protein on lagging chromosomes. Proc Natl Acad Sci USA 1999; 96: 8493-8498.Google Scholar
  66. 66.
    Shannon KB, Salmon ED. Chromosome dynamics: New light on AuroraBkinase function. Curr Biol 2002; 12: R458-R460.Google Scholar
  67. 67.
    Jordan MA, Wilson L. Microtubules and actin filaments: Dynamic targets for cancer chemotherapy. Curr Opin Cell Biol 1998; 10: 123-130.Google Scholar
  68. 68.
    Janmey PA. The cytoskeleton and cell signaling: Component localization and mechanical coupling. Physiol Rev 1998; 78: 763-781.Google Scholar
  69. 69.
    Liu XM, Wang LG, Kreis W, Budman DR, Adams LM. Differential effect of vinorelbine versus paclitaxel onERK2kinase activity during apoptosis in MCF-7 cells. Br J Cancer 2001; 85: 1403-1411.Google Scholar
  70. 70.
    Wendell KL, Wilson L, Jordan MA. Mitotic block in HeLa cells by vinblastine: Ultrastructural changes in kinetochoremicrotubule attachment and in centrosomes. J Cell Sci 1993; 104(Pt 2): 261-274.Google Scholar
  71. 71.
    Jordan MA, Thrower D, Wilson L. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis. J Cell Sci 1992; 102: 401-416.Google Scholar
  72. 72.
    Fukasawa K, Choi T, Kuriyama R, Rulong S, Vande Woude GF. Abnormal centrosome amplification in the absence of p53. Science 1996; 271: 1744-1747.Google Scholar
  73. 73.
    Wahl AF, Donaldson KL, Fairchild C, et al. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med 1996; 2: 72-79.Google Scholar
  74. 74.
    Vikhanskaya F, Vignati S, Beccaglia P, et al. Inactivation of p53 in a human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis. Exp Cell Res 1998; 241: 96-101.Google Scholar
  75. 75.
    Bosch I, Croop J. P-glycoprotein multidrug resistance and cancer. Biochim Biophys Acta 1996; 1288: F37-F54.Google Scholar
  76. 76.
    Loe DW, Deeley RG, Cole SP. Biology of the multidrug resistance-associated protein, MRP. Eur J Cancer 1996; 32A: 945-957.Google Scholar
  77. 77.
    Izquierdo MA, Scheffer GL, Flens MJ, et al. Major vault protein LRP-related multidrug resistance. Eur J Cancer 1996; 32A: 979-984.Google Scholar
  78. 78.
    Wilson L, Jordan MA. Microtubule dynamics: Taking aim at a moving target. Chem Biol 1995; 2: 569-573.Google Scholar
  79. 79.
    Cui CB, Kakeya H, Okada G, et al. Tryprostatins A and B, novel mammalian cell cycle inhibitors produced by Aspergillus fumigatus. J Antibiot (Tokyo) 1995; 48: 1382-1384.Google Scholar
  80. 80.
    Usui T, Kondoh M, Cui CB, Mayumi T, Osada H. Tryprostatin A, a specific and novel inhibitor of microtubule assembly. Biochem J 1998; 333: 543-548.Google Scholar
  81. 81.
    Osada H. Development and application of bioprobes forMammalian cell cycle analyses. Curr Med Chem 2003; 10: 727-732.Google Scholar
  82. 82.
    Pettit GR, Kamano Y, Fujii Y, et al. Marine animal biosynthetic constituents for cancer chemotherapy. J Nat Prod 1981; 44: 482-485.Google Scholar
  83. 83.
    Bai R, Pettit GR, Hamel E. Dolastatin 10, a powerful cytostatic peptide derived from a marine animal. Inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain. Biochem Pharmacol 1990; 39: 1941-1949.Google Scholar
  84. 84.
    Bai R, Friedman SJ, Pettit GR, Hamel E. Dolastatin 15, a potent antimitotic depsipeptide derived from Dolabella auricularia. Interaction with tubulin and effects of cellular microtubules. Biochem Pharmacol 1992; 43: 2637-2645.Google Scholar
  85. 85.
    Hamel E. Natural products which interact with tubulin in the vinca domain: Maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B. Pharmacol Ther 1992; 55: 31-51.Google Scholar
  86. 86.
    Pettit GR. The dolastatins. Fortschr Chem Org Naturst 1997; 70: 1-79.Google Scholar
  87. 87.
    Poncet J. The dolastatins, a family of promising antineoplastic agents. Curr Pharm Des 1999; 5: 139-162.Google Scholar
  88. 88.
    Newman RA, Fuentes A, Covey JM, Benvenuto JA. Preclinical pharmacology of the natural marine product dolastatin 10 (NSC 376128). Drug Metab Dispos 1994; 22: 428-432.Google Scholar
  89. 89.
    Pathak S, Multani AS, Ozen M, Richardson MA, Newman RA. Dolastatin-10 induces polyploidy, telomeric associations and apoptosis in a murine melanoma cell line. Oncol Rep 1998; 5: 373-376.Google Scholar
  90. 90.
    Mirsalis JC, Schindler-Horvat J, Hill JR, et al. Toxicity of dolastatin 10 in mice, rats and dogs and its clinical relevance. Cancer Chemother Pharmacol 1999; 44: 395-402.Google Scholar
  91. 91.
    Wright JJ, Blatner G, Cheson BD. Clinical trials referral resource. Clinical trials of dolastatin-10. Oncology (Huntingt) 1999; 13: 68-70, 75.Google Scholar
  92. 92.
    Pitot HC, McElroy EA Jr, Reid JM, et al. Phase I trial of dolastatin-10 (NSC 376128) in patients with advanced solid tumors. Clin Cancer Res 1999; 5: 525-531.Google Scholar
  93. 93.
    Margolin K, Longmate J, Synold TW, et al. Dolastatin-10 in metastatic melanoma: A phase II and pharmokinetic trial of the California Cancer Consortium. Invest New Drugs 2001; 19: 335-340.Google Scholar
  94. 94.
    Vaishampayan U, Glode M, Du W, et al. Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma. Clin Cancer Res 2000; 6: 4205-4208.Google Scholar
  95. 95.
    Krug LM, Miller VA, Kalemkerian GP, et al. Phase II study of dolastatin-10 in patients with advanced non-small-cell lung cancer. Ann Oncol 2000; 11: 227-228.Google Scholar
  96. 96.
    Saad ED, Kraut EH, Hoff PM, et al. Phase II study of dolastatin-10 as first-line treatment for advanced colorectal cancer. Am J Clin Oncol 2002; 25: 451-453.Google Scholar
  97. 97.
    Thamm DH, MacEwen EG, Phillips BS, et al. Preclinical study of dolastatin-10 in dogs with spontaneous neoplasia. Cancer Chemother Pharmacol 2002; 49: 251-255.Google Scholar
  98. 98.
    Otani M, Natsume T, Watanabe JI, et al. TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death. Jpn J Cancer Res 2000; 91: 837-844.Google Scholar
  99. 99.
    Luesch H, Yoshida WY, Moore RE, et al. Symplostatin 3, a new dolastatin 10 analogue from the marine cyanobacterium Symploca sp. VP452. J Nat Prod 2002; 65: 16-20.Google Scholar
  100. 100.
    Mooberry SL, Leal RM, Tinley TL, et al. The molecular pharmacology of symplostatin 1: A new antimitotic dolastatin 10 analog. Int J Cancer 2003; 104: 512-521.Google Scholar
  101. 101.
    Kerbrat P, Dieras V, Pavlidis N, et al. Phase II study of LU 103793 (dolastatin analogue) in patients with metastatic breast cancer. Eur J Cancer 2003; 39: 317-320.Google Scholar
  102. 102.
    Smith CD, Zhang X, Mooberry SL, Patterson GM, Moore RE. Cryptophycin: A new antimicrotubule agent active against drug-resistant cells. Cancer Res 1994; 54: 3779-3784.Google Scholar
  103. 103.
    Kerksiek K, Mejillano MR, Schwartz RE, Georg GI, Himes RH. Interaction of cryptophycin 1 with tubulin and microtubules. FEBS Lett 1995; 377: 59-61.Google Scholar
  104. 104.
    Smith CD, Zhang X. Mechanism of action cryptophycin. Interaction with the Vinca alkaloid domain of tubulin. J Biol Chem 1996; 271: 6192-6198.Google Scholar
  105. 105.
    Mooberry SL, Taoka CR, Busquets L. Cryptophycin 1 binds to tubulin at a site distinct from the colchicine binding site and at a site that may overlap the vinca binding site. Cancer Lett 1996; 107: 53-57.Google Scholar
  106. 106.
    Panda D, Himes RH, Moore RE, Wilson L, Jordan MA. Mechanism of action of the unusually potent microtubule inhibitor cryptophycin 1. Biochemistry 1997; 36: 12948-12953.Google Scholar
  107. 107.
    Mooberry SL, Busquets L, Tien G. Induction of apoptosis by cryptophycin 1, a new antimicrotubule agent. Int J Cancer 1997; 73: 440-448.Google Scholar
  108. 108.
    Shih C, Teicher BA. Cryptophycins: A novel class of potent antimitotic antitumor depsipeptides. Curr Pharm Des 2001; 7: 1259-1276.Google Scholar
  109. 109.
    Corbett TH, Valeriote FA, Demchik L, et al. Preclinical anticancer activity of cryptophycin-8. J Exp Ther Oncol 1996; 1: 95-108.Google Scholar
  110. 110.
    Patel VF, Andis SL, Kennedy JH, Ray JE, Schultz RM. Novel cryptophycin antitumor agents: Synthesis and cytotoxicity of fragment “B” analogues. J Med Chem 1999; 42: 2588-2603.Google Scholar
  111. 111.
    Wagner MM, Paul DC, Shih C, et al. In vitro pharmacology of cryptophycin 52 (LY355703) in human tumor cell lines. Cancer Chemother Pharmacol 1999; 43: 115-125.Google Scholar
  112. 112.
    Sessa C, Weigang-Kohler K, Pagani O, et al. Phase I and pharmacological studies of the cryptophycin analogue LY355703 administered on a single intermittent or weekly schedule. Eur J Cancer 2002; 38: 2388-2396.Google Scholar
  113. 113.
    Edelman MJ, Gandara DR, Hausner P, et al. Phase 2 study of cryptophycin 52 (LY355703) in patients previously treated with platinum based chemotherapy for advanced non-small cell lung cancer. Lung Cancer 2003; 39: 197-199.Google Scholar
  114. 114.
    Hastie SB. Interactions of colchicine with tubulin. Pharmacol Ther 1991; 51: 377-401.Google Scholar
  115. 115.
    Shearwin KE, Timasheff SN. Effect of colchicine analogues on the dissociation of alpha beta tubulin into subunits: The locus of colchicine binding. Biochemistry 1994; 33: 894-901.Google Scholar
  116. 116.
    Menendez M, Rivas G, Diaz JF, Andreu JM. Control of the structural stability of the tubulin dimer by one high affinity bound magnesium ion at nucleotide N-site. J Biol Chem 1998; 273: 167-176.Google Scholar
  117. 117.
    Chaudhuri AR, Seetharamalu P, Schwarz PM, Hausheer FH, Luduena RF. The interaction of the B-ring of colchicine with alpha-tubulin: A novel footprinting approach. J Mol Biol 2000; 303: 679-692.Google Scholar
  118. 118.
    Andreu JM, Timasheff SN. Interaction of tubulin with single ring analogues of colchicine. Biochemistry 1982; 21: 534-543.Google Scholar
  119. 119.
    Andreu JM, Perez-Ramirez B, Gorbunoff MJ, Ayala D, Timasheff SN. Role of the colchicine ring A and its methoxy groups in the binding to tubulin and microtubule inhibition. Biochemistry 1998; 37: 8356-8368.Google Scholar
  120. 120.
    Perez-Ramirez B, Andreu JM, Gorbunoff MJ, Timasheff SN. Stoichiometric and substoichiometric inhibition of tubulin self-assembly by colchicine analogues. Biochemistry 1996; 35: 3277-3285.Google Scholar
  121. 121.
    Perez-Ramirez B, Gorbunoff MJ, Timasheff SN. Linkages in tubulin-colchicine functions: The role of the ring C (C′) oxygens and ring B in the controls. Biochemistry 1998; 37: 1646-1661.Google Scholar
  122. 122.
    Duncan AM, Heddle JA. The frequency and distribution of apoptosis induced by three non-carcinogenic agents in mouse colonic crypts. Cancer Lett 1984; 23: 307-311.Google Scholar
  123. 123.
    Martin SJ, Cotter TG. Specific loss of microtubules in HL-60 cells leads to programmed cell death (apoptosis). Biochem Soc Trans 1990; 18: 299-301.Google Scholar
  124. 124.
    Martin SJ, Bonham AM, Cotter TG. The involvement ofRNA and protein synthesis in programmed cell death (apoptosis) in human leukaemia HL-60 cells. Biochem Soc Trans 1990; 18: 634-636.Google Scholar
  125. 125.
    Martin SJ, Lennon SV, Bonham AM, Cotter TG. Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis. J Immunol 1990; 145: 1859-1867.Google Scholar
  126. 126.
    Bonfoco E, Ceccatelli S, Manzo L, Nicotera P. Colchicine induces apoptosis in cerebellar granule cells. Exp Cell Res 1995; 218: 189-200.Google Scholar
  127. 127.
    De Vincenzo R, Scambia G, Ferlini C, et al. Antiproliferative activity of colchicine analogues on MDR-positive and MDRnegative human cancer cell lines. Anticancer Drug Des 1998; 13: 19-33.Google Scholar
  128. 128.
    Brewton LS, Haddad L, Azmitia EC. Colchicine-induced cytoskeletal collapse and apoptosis in N-18 neuroblastoma cultures is rapidly reversed by applied S-100beta. Brain Res 2001; 912: 9-16.Google Scholar
  129. 129.
    Fakih M, Yagoda A, Replogle T, Lehr JE, Pienta KJ. Inhibition of prostate cancer growth by estramustine and colchicine. Prostate 1995; 26: 310-315.Google Scholar
  130. 130.
    Sun L, Hamel E, Lin CM, et al. Antitumor agents. 141. Synthesis and biological evaluation of novel thiocolchicine analogs: N-acyl-, N-aroyl-, and N-(substituted benzyl)deacetylthiocolchicines as potent cytotoxic and antimitotic compounds. J Med Chem 1993; 36: 1474-1479.Google Scholar
  131. 131.
    Sun L, McPhail AT, Hamel E, et al. Antitumor agents. 139. Synthesis and biological evaluation of thiocolchicine analogs 5,6-dihydro-6(S)-(acyloxy)-and 5,6-dihydro-6(S)-[(aroyloxy) methyl]-1,2,3-trimethoxy-9-(methylthio)-8Hcyclohepta[ a]naphthalen-8-ones as novel cytotoxic and antimitotic agents. J Med Chem 1993; 36: 544-551.Google Scholar
  132. 132.
    Ueda K, Cardarelli C, Gottesman MM, Pastan I. Expression of a full-length cDNA for the human “MDR1” gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 1987; 84: 3004-3008.Google Scholar
  133. 133.
    Ringel I, Jaffe D, Alerhand S, et al. Fluorinated colchicinoids: Antitubulin and cytotoxic properties. J Med Chem 1991; 34: 3334-3338.Google Scholar
  134. 134.
    Fitzgerald TJ. Molecular features of colchicine associated with antimitotic activity and inhibition of tubulin polymerization. Biochem Pharmacol 1976; 25: 1383-1387.Google Scholar
  135. 135.
    Andreu JM, Gorbunoff MJ, Lee JC, Timasheff SN. Interaction of tubulin with bifunctional colchicine analogues: An equilibrium study. Biochemistry 1984; 23: 1742-1752.Google Scholar
  136. 136.
    Bane S, Puett D, Macdonald TL, Williams RC Jr. Binding to tubulin of the colchicine analog 2-methoxy-5-(2′, 3′, 4′-trimethoxyphenyl)tropone. Thermodynamic and kinetic aspects. J Biol Chem 1984; 259: 7391-7398.Google Scholar
  137. 137.
    Engelborghs Y, Fitzgerald TJ. A fluorescence stopped flow study of the competition and displacement kinetics of podophyllotoxin and the colchicine analog 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl) tropone on tubulin. J Biol Chem 1987; 262: 5204-5209.Google Scholar
  138. 138.
    Diez JC, Avila J, Nieto JM, Andreu JM. Reversible inhibition of microtubules and cell growth by the bicyclic colchicine analogue MTC. Cell Motil Cytoskeleton 1987; 7: 178-186.Google Scholar
  139. 139.
    Mollinedo F, Nieto JM, Andreu JM. Cytoplasmic microtubules in human neutrophil degranulation: Reversible inhibition by the colchicine analogue 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one. Mol Pharmacol 1989; 36: 547-555.Google Scholar
  140. 140.
    Gajate C, Barasoain I, Andreu JM, Mollinedo F. Induction of apoptosis in leukemic cells by the reversible microtubuledisrupting agent 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one: Protection by Bcl-2 and Bcl-X(L) and cell cycle arrest. Cancer Res 2000; 60: 2651-2659.Google Scholar
  141. 141.
    De Brabander MJ, Van de Veire RM, Aerts FE, Borgers M, Janssen PA. The effects of methyl (5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl) carbamate, (R 17934; NSC 238159), a new synthetic antitumoral drug interfering with microtubules, on mammalian cells cultured in vitro. Cancer Res 1976; 36: 905-916.Google Scholar
  142. 142.
    De Clerck F, De Brabander M. Nocodazole, a new synthetic antimitotic agent, enhances the production of plasminogen activator by cells in culture. Thromb Res 1977; 11: 913-914.Google Scholar
  143. 143.
    Hamilton BT, Snyder JA. Rapid completion of mitosis and cytokinesis in PtK cells following release from nocodazole arrest. Eur J Cell Biol 1982; 28: 190-194.Google Scholar
  144. 144.
    Sackett DL. Podophyllotoxin, steganacin and combretastatin: Natural products that bind at the colchicine site of tubulin. Pharmacol Ther 1993; 59: 163-228.Google Scholar
  145. 145.
    Lin CM, Ho HH, Pettit GR, Hamel E. Antimitotic natural products combretastatin A-4 and combretastatin A-2: Studies on the mechanism of their inhibition of the binding of colchicine to tubulin. Biochemistry 1989; 28: 6984-6991.Google Scholar
  146. 146.
    Griggs J, Metcalfe JC, Hesketh R. Targeting tumour vasculature: The development of combretastatin A4. Lancet Oncol 2001; 2: 82-87.Google Scholar
  147. 147.
    Lin CM, Singh SB, Chu PS, et al. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: A structure-activity study. Mol Pharmacol 1988; 34: 200-208.Google Scholar
  148. 148.
    Blokhin AV, Yoo HD, Geralds RS, et al. Characterization of the interaction of the marine cyanobacterial natural product curacin A with the colchicine site of tubulin and initial structure-activity studies with analogues. Mol Pharmacol 1995; 48: 523-531.Google Scholar
  149. 149.
    Verdier-Pinard P, Sitachitta N, Rossi JV, et al. Biosynthesis of radiolabeled curacin A and its rapid and apparently irreversible binding to the colchicine site of tubulin. Arch Biochem Biophys 1999; 370: 51-58.Google Scholar
  150. 150.
    Leoni LM, Hamel E, Genini D, et al. Indanocine, a microtubule-binding indanone and a selective inducer of apoptosis in multidrug-resistant cancer cells. J Natl Cancer Inst 2000; 92: 217-224.Google Scholar
  151. 151.
    Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 1971; 93: 2325-2327.Google Scholar
  152. 152.
    Rowinsky EK, Cazenave LA, Donehower RC. Taxol: A novel investigational antimicrotubule agent. J Natl Cancer Inst 1990; 82: 1247-1259.Google Scholar
  153. 153.
    Bhalla K, Ibrado AM, Tourkina E, et al. Taxol induces internucleosomal DNA fragmentation associated with programmed cell death in human myeloid leukemia cells. Leukemia 1993; 7: 563-568.Google Scholar
  154. 154.
    Li X, Gong J, Feldman E, et al. Apoptotic cell death during treatment of leukemias. Leuk Lymphoma 1994; 13(Suppl 1): 65-70.Google Scholar
  155. 155.
    Moos PJ, Fitzpatrick FA. Taxanes propagate apoptosis via two cell populations with distinctive cytological and molecular traits. Cell Growth Differ 1998; 9: 687-697.Google Scholar
  156. 156.
    Shen SC, Huang TS, Jee SH, Kuo ML. Taxol-induced p34cdc2 kinase activation and apoptosis inhibited by 12-O-tetradecanoylphorbol-13-acetate in human breast MCF-7 carcinoma cells. Cell Growth Differ 1998; 9: 23-29.Google Scholar
  157. 157.
    Debernardis D, Sire EG, De Feudis P, et al. p53 status does not affect sensitivity of human ovarian cancer cell lines to paclitaxel. Cancer Res 1997; 57: 870-874.Google Scholar
  158. 158.
    Zhang Z, Liu Q, Lantry LE, et al. A germ-line p53 mutation accelerates pulmonary tumorigenesis: p53-independent efficacy of chemopreventive agents green tea or dexamethasone/myo-inositol and chemotherapeutic agents taxol or adriamycin. Cancer Res 2000; 60: 901-907.Google Scholar
  159. 159.
    Wilson L, Bamburg JR, Mizel SB, Grisham LM, Creswell KM. Interaction of drugs with microtubule proteins. Fed Proc 1974; 33: 158-166.Google Scholar
  160. 160.
    Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979; 277: 665-667.Google Scholar
  161. 161.
    Manfredi JJ, Horwitz SB. Taxol: An antimitotic agent with a new mechanism of action. Pharmacol Ther 1984; 25: 83-125.Google Scholar
  162. 162.
    Schiff PB, Horwitz SB.Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 1980; 77: 1561-1565.Google Scholar
  163. 163.
    Wang TH, Popp DM, Wang HS, et al. Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun N-terminal kinase (JNK)-dependent and-independent pathways in ovarian cancer cells. J Biol Chem 1999; 274: 8208-8216.Google Scholar
  164. 164.
    Kottke TJ, Blajeski AL, Martins LM, et al. Comparison of paclitaxel-, 5-fluoro-2′-deoxyuridine-, and epidermal growth factor (EGF)-induced apoptosis. Evidence for EGF-induced anoikis. J Biol Chem 1999; 274: 15927-15936.Google Scholar
  165. 165.
    Jordan MA, Wendell K, Gardiner S, et al. Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res 1996; 56: 816-825.Google Scholar
  166. 166.
    Torres K, Horwitz SB. Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res 1998; 58: 3620-3626.Google Scholar
  167. 167.
    Wang TH, Wang HS, Soong YK. Paclitaxel-induced cell death: Where the cell cycle and apoptosis come together. Cancer 2000; 88: 2619-2628.Google Scholar
  168. 168.
    Yvon AM, Wadsworth P, Jordan MA. Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol Biol Cell 1999; 10: 947-959.Google Scholar
  169. 169.
    Woods CM, Zhu J, McQueney PA, Bollag D, Lazarides E. Taxol-induced mitotic block triggers rapid onset of a p53-independent apoptotic pathway. Mol Med 1995; 1: 506-526.Google Scholar
  170. 170.
    Lin HL, Chang YF, Liu6TY, Wu CW, Chi CW. Submicromolar paclitaxel induces apoptosis in human gastric cancer cells at early G1 phase. Anticancer Res 1998; 18: 3443-3449.Google Scholar
  171. 171.
    Rao S, He L, Chakravarty S, et al. Characterization of the Taxol binding site on the microtubule. Identification of Arg(282) in beta-tubulin as the site of photoincorporation of a 7-benzophenone analogue of Taxol. J Biol Chem 1999; 274: 37990-37994.Google Scholar
  172. 172.
    Parness J, Horwitz SB. Taxol binds to polymerized tubulin in vitro. J Cell Biol 1981; 91: 479-487.Google Scholar
  173. 173.
    Diaz JF, Andreu JM. Assembly of purified GDP-tubulin into microtubules induced by taxol and taxotere: Reversibility, ligand stoichiometry, and competition. Biochemistry 1993; 32: 2747-2755.Google Scholar
  174. 174.
    Caplow M, Shanks J, Ruhlen R. How taxol modulates microtubule disassembly. J Biol Chem 1994; 269: 23399-23402.Google Scholar
  175. 175.
    Stein CA. Mechanisms of action of taxanes in prostate cancer. Semin Oncol 1999; 26: 3-7.Google Scholar
  176. 176.
    Rowinsky EK, Eisenhauer EA, Chaudhry V, Arbuck SG, Donehower RC. inical toxicities encountered with paclitaxel (Taxol). Semin Oncol 1993; 20: 1-15.Google Scholar
  177. 177.
    Chaudhry V, Rowinsky EK, Sartorius SE, Donehower RC, Cornblath DR. Peripheral neuropathy from taxol and cisplatin combination chemotherapy: Clinical and electrophysiological studies. Ann Neurol 1994; 35: 304-311.Google Scholar
  178. 178.
    Ojima I, Slater JC, Michaud E, et al. Syntheses and structureactivity relationships of the second-generation antitumor taxoids: Exceptional activity against drug-resistant cancer cells. J Med Chem 1996; 39: 3889-3896.Google Scholar
  179. 179.
    Jordan MA, Ojima I, Rosas F, et al. Effects of novel taxanes SBT-1213 and IDN5109 on tubulin polymerization and mitosis. Chem Biol 2002; 9: 93-101.Google Scholar
  180. 180.
    Ferlini C, Distefano M, Pignatelli F, et al. Antitumour activity of novel taxanes that act at the same time as cytotoxic agents and P-glycoprotein inhibitors. Br J Cancer 2000; 83: 1762-1768.Google Scholar
  181. 181.
    Gerth K, Bedorf N, Hofle G, Irschik H, Reichenbach H. Epothilons A and B: Antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties. J Antibiot (Tokyo) 1996; 49: 560-563.Google Scholar
  182. 182.
    Gerth K, Steinmetz H, Hoflel G, Reichenbach H. Studies on the biosynthesis of epothilones: Hydroxylation of Epo A and B to epothilones E and F. J Antibiot (Tokyo) 2002; 55: 41-45.Google Scholar
  183. 183.
    Hardt IH, Steinmetz H, Gerth K, et al. New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13: Isolation, structure elucidation, and SAR studies. J Nat Prod 2001; 64: 847-856.Google Scholar
  184. 184.
    Pradella S, Hans A, Sproer C, et al. Characterisation, genome size and genetic manipulation of the myxobacterium Sorangium cellulosum So ce56. Arch Microbiol 2002; 178: 484-492.Google Scholar
  185. 185.
    Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 1995; 55: 2325-2333.Google Scholar
  186. 186.
    Altmann KH, Wartmann M, O'Reilly T. Epothilones and related structures-A new class of microtubule inhibitors with potent in vivo antitumor activity. Biochim Biophys Acta 2000; 1470: M79-M91.Google Scholar
  187. 187.
    Badary OA, Al-Shabanah OA, Al-Gharably NM, Elmazar MM. Effect of Cremophor EL on the pharmacokinetics, antitumor activity and toxicity of doxorubicin in mice. Anticancer Drugs 1998; 9: 809-815.Google Scholar
  188. 188.
    ter Haar E, Kowalski RJ, Hamel E, et al. Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemistry 1996; 35: 243-250.Google Scholar
  189. 189.
    Kowalski RJ, Giannakakou P, Gunasekera SP, et al. The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells. Mol Pharmacol 1997; 52: 613-622.Google Scholar
  190. 190.
    Longley RE, Caddigan D, Harmody D, Gunasekera M, Gunasekera SP. Discodermolide-A new, marine-derived immunosuppressive compound. II. In vivo studies. Transplantation 1991; 52: 656-661.Google Scholar
  191. 191.
    Longley RE, Gunasekera SP, Faherty D, McLane J, Dumont F. Immunosuppression by discodermolide. Ann N Y Acad Sci 1993; 696: 94-107.Google Scholar
  192. 192.
    Hung DT, Nerenberg JB, Schreiber SL. Distinct binding and cellular properties of synthetic (+)-and (-)-discodermolides. Chem Biol 1994; 1: 67-71.Google Scholar
  193. 193.
    Balachandran R, ter Haar E, Welsh MJ, Grant SG, Day BW. The potent microtubule-stabilizing agent (+)-discodermolide induces apoptosis in human breast carcinoma cells-Preliminary comparisons to paclitaxel. Anticancer Drugs 1998; 9: 67-76.Google Scholar
  194. 194.
    Gunasekera SP, Paul GK, Longley RE, Isbrucker RA, Pomponi SA. Five new discodermolide analogues from the marine sponge Discodermia species. J Nat Prod 2002; 65: 1643-1648.Google Scholar
  195. 195.
    Gunasekera SP, Longley RE, Isbrucker RA. Semisynthetic analogues of the microtubule-stabilizing agent discodermolide: Preparation and biological activity. J Nat Prod 2002; 65: 1830-1837.Google Scholar
  196. 196.
    Long BH, Carboni JM, Wasserman AJ, et al. Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). Cancer Res 1998; 58: 1111-1115.Google Scholar
  197. 197.
    Mooberry SL, Tien G, Hernandez AH, Plubrukarn A, Davidson BS. Laulimalide and isolaulimalide, new paclitaxellike microtubule-stabilizing agents. Cancer Res 1999; 59: 653-660.Google Scholar
  198. 198.
    Moraga D, Rivas-Berrios A, Farias G, Wallin M, Maccioni RB. Estramustine-phosphate binds to a tubulin binding domain on microtubule-associated proteins MAP-2 and tau. Biochim Biophys Acta 1992; 1121: 97-103.Google Scholar
  199. 199.
    Dahllof B, Billstrom A, Cabral F, Hartley-Asp B. Estramustine depolymerizes microtubules by binding to tubulin. Cancer Res 1993; 53: 4573-4581.Google Scholar
  200. 200.
    Wallin M, Deinum J, Friden B. Interaction of estramustine phosphate with microtubule-associated proteins. FEBS Lett 1985; 179: 289-293.Google Scholar
  201. 201.
    Stearns ME, Tew KD. Estramustine binds MAP-2 to inhibit microtubule assembly in vitro. J Cell Sci 1988; 89: 331-342.Google Scholar
  202. 202.
    Stearns ME, Wang M, Tew KD, Binder LI. Estramustine binds a MAP-1-like protein to inhibit microtubule assembly in vitro and disrupt microtubule organization in DU 145 cells. J Cell Biol 1988; 107: 2647-2656.Google Scholar
  203. 203.
    Liu QY, Stein CA. Taxol and estramustine-induced modulation of human prostate cancer cell apoptosis via alteration in bcl-xL and bak expression. Clin Cancer Res 1997; 3: 2039-2046.Google Scholar
  204. 204.
    Vallbo C, Bergenheim AT, Bergstrom P, Gunnarsson PO, Henriksson R. Apoptotic tumor cell death induced by estramustine in patients with malignant glioma. Clin Cancer Res 1998; 4: 87-91.Google Scholar
  205. 205.
    Yoshida D, Noha M, Watanabe K, et al. Induction of apoptosis by estramustine phosphate mediated by phosphorylation of bcl-2. J Neurooncol 2001; 54: 23-29.Google Scholar
  206. 206.
    Vallbo C, Bergenheim T, Hedman H, Henriksson R. The antimicrotubule drug estramustine but not irradiation induces apoptosis in malignant glioma involving AKT and caspase pathways. J Neurooncol 2002; 56: 143-148.Google Scholar
  207. 207.
    Hudes GR, Obasaju C, Chapman A, et al. Phase I study of paclitaxel and estramustine: Preliminary activity in hormonerefractory prostate cancer. Semin Oncol 1995; 22: 6-11.Google Scholar
  208. 208.
    Sewak S, Chachoua A, Hamilton A, et al. A phase I study of paclitaxel, estramustine phosphate and vinorelbine (Pacl-E-Vin) in advanced malignancies: Triple tubulin targeting. Anticancer Drugs 2003; 14: 67-72.Google Scholar
  209. 209.
    Bergenheim AT, Henriksson R, Piepmeier JM, Yoshida D. Estramustine in malignant glioma. J Neurooncol 1996; 30: 81-89.Google Scholar
  210. 210.
    Sangrajrang S, Calvo F, Fellous A. Estramustine resistance. Gen Pharmacol 1999; 33: 107-113.Google Scholar
  211. 211.
    Donaldson KL, Goolsby GL, Kiener PA, Wahl AF. Activation of p34cdc2 coincident with taxol-induced apoptosis. Cell Growth Differ 1994; 5: 1041-1050.Google Scholar
  212. 212.
    Long BH, Fairchild CR. Paclitaxel inhibits progression of mitotic cells to G1 phase by interference with spindle formation without affecting other microtubule functions during anaphase and telephase. Cancer Res 1994; 54: 4355-4361.Google Scholar
  213. 213.
    Raff MC. Social controls on cell survival and cell death. Nature 1992; 356: 397-400.Google Scholar
  214. 214.
    Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309-1312.Google Scholar
  215. 215.
    Adams JM, Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998; 281: 1322-1326.Google Scholar
  216. 216.
    Antonsson B, Martinou JC. The Bcl-2 protein family. Exp Cell Res 2000; 256: 50-57.Google Scholar
  217. 217.
    Adams JM, Cory S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem Sci 2001; 26: 61-66.Google Scholar
  218. 218.
    Ranger AM, Malynn BA, Korsmeyer SJ. Mouse models of cell death. Nat Genet 2001; 28: 113-118.Google Scholar
  219. 219.
    Gross A, McDonnell JM, Korsmeyer SJ. BCL-2 family members and the mitochondria in apoptosis. Genes Dev 1999; 13: 1899-1911.Google Scholar
  220. 220.
    Ke N, Godzik A, Reed JC. Bcl-B, a novel Bcl-2 family member that differentially binds and regulates Bax and Bak. J Biol Chem 2001; 276: 12481-12484.Google Scholar
  221. 221.
    Ibrado AM, Huang Y, Fang G, Bhalla K. Bcl-xL overexpression inhibits taxol-induced Yama protease activity and apoptosis. Cell Growth Differ 1996; 7: 1087-1094.Google Scholar
  222. 222.
    Tang C, Willingham MC, Reed JC, et al. High levels of p26BCL-2 oncoprotein retard taxol-induced apoptosis in human pre-B leukemia cells. Leukemia 1994; 8: 1960-1969.Google Scholar
  223. 223.
    Ibrado AM, Liu L, Bhalla K. Bcl-xL overexpression inhibits progression of molecular events leading to paclitaxel-induced apoptosis of human acute myeloid leukemia HL-60 cells. Cancer Res 1997; 57: 1109-1115.Google Scholar
  224. 224.
    Inohara N, Ding L, Chen S, Nunez G. Harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). EMBO J 1997; 16: 1686-1694.Google Scholar
  225. 225.
    Puthalakath H, Villunger A, O'Reilly LA, et al. Bmf: A proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science 2001; 293: 1829-1832.Google Scholar
  226. 226.
    Kataoka T, Holler N, Micheau O, et al. Bcl-rambo, a novel Bcl-2 homologue that induces apoptosis via its unique C-terminal extension. J Biol Chem 2001; 276: 19548-19554.Google Scholar
  227. 227.
    Guo B, Godzik A, Reed JC. Bcl-G, a novel pro-apoptotic member of the Bcl-2 family. J Biol Chem 2001; 276: 2780-2785.Google Scholar
  228. 228.
    Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 2001; 7: 683-694.Google Scholar
  229. 229.
    Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A. The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Mol Cell 1999; 3: 287-296.Google Scholar
  230. 230.
    Hsu YT, Youle RJ. Bax in murine thymus is a soluble monomeric protein that displays differential detergentinduced conformations. J Biol Chem 1998; 273: 10777-10783.Google Scholar
  231. 231.
    Cheng EH, Wei MC, Weiler S, et al. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX-and BAK-mediated mitochondrial apoptosis. Mol Cell 2001; 8: 705-711.Google Scholar
  232. 232.
    Zong WX, Lindsten T, Ross AJ, MacGregor GR, Thompson CB. BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and Bak. Genes Dev 2001; 15: 1481-1486.Google Scholar
  233. 233.
    Desagher S, Osen-Sand A, Nichols A, et al. Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis. J Cell Biol 1999; 144: 891-901.Google Scholar
  234. 234.
    Kelekar A, Thompson CB. Bcl-2-family proteins: The role of the BH3 domain in apoptosis. Trends Cell Biol 1998; 8: 324-330.Google Scholar
  235. 235.
    Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74: 609-619.Google Scholar
  236. 236.
    Chittenden T, Harrington EA, O'Connor R, et al. Induction of apoptosis by the Bcl-2 homologue Bak. Nature 1995; 374: 733-736.Google Scholar
  237. 237.
    Knudson CM, Korsmeyer SJ. Bcl-2 and Bax function independently to regulate cell death. Nat Genet 1997; 16: 358-363.Google Scholar
  238. 238.
    O'Connor L, Strasser A, O'Reilly LA, et al. Bim: A novel member of the Bcl-2 family that promotes apoptosis. EMBO J 1998; 17: 384-395.Google Scholar
  239. 239.
    Bouillet P, Metcalf D, Huang DC, et al. Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 1999; 286: 1735-1738.Google Scholar
  240. 240.
    Bouillet P, Purton JF, Godfrey DI, et al. BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 2002; 415: 922-926.Google Scholar
  241. 241.
    Villunger A, Scott C, Bouillet P, Strasser A. Essential role for the BH3-only protein Bim but redundant roles for Bax, Bcl-2, and Bcl-w in the control of granulocyte survival. Blood 2003; 101: 2393-2400.Google Scholar
  242. 242.
    Putcha GV, Moulder KL, Golden JP, et al. Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is critical for neuronal apoptosis. Neuron 2001; 29: 615-628.Google Scholar
  243. 243.
    O'Reilly LA, Cullen L, Visvader J, et al. The proapoptotic BH3-only protein bim is expressed in hematopoietic, epithelial, neuronal, and germ cells. Am J Pathol 2000; 157: 449-461.Google Scholar
  244. 244.
    UM, Miyashita T, Shikama Y, Tadokoro K, Yamada M. Molecular cloning and characterization of six novel isoforms of human Bim, a member of the proapoptotic Bcl-2 family. FEBS Lett 2001; 509: 135-141.Google Scholar
  245. 245.
    Liu JW, Chandra D, Tang SH, Chopra D, Tang DG. Identification and characterization of Bimgamma, a novel proapoptotic BH3-only splice variant of Bim. Cancer Res 2002; 62: 2976-2981.Google Scholar
  246. 246.
    Marani M, Tenev T, Hancock D, Downward J, Lemoine NR. Identification of novel isoforms of the BH3 domain protein Bim which directly activate Bax to trigger apoptosis. Mol Cell Biol 2002; 22: 3577-3589.Google Scholar
  247. 247.
    Grossmann J. Molecular mechanisms of “detachment-induced apoptosis-Anoikis.” Apoptosis 2002; 7: 247-260.Google Scholar
  248. 248.
    Gilmore AP, Metcalfe AD, Romer LH, Streuli CH. Integrinmediated survival signals regulate the apoptotic function of Bax through its conformation and subcellular localization. J Cell Biol 2000; 149: 431-446.Google Scholar
  249. 249.
    Murphy KM, Streips UN, Lock RB. Bcl-2 inhibits a Fasinduced conformational change in the Bax N terminus and Bax mitochondrial translocation. J Biol Chem 2000; 275: 17225-17228.Google Scholar
  250. 250.
    Terradillos O, Montessuit S, Huang DC, Martinou JC. Direct addition of BimL to mitochondria does not lead to cytochrome c release. FEBS Lett 2002; 522: 29-34.Google Scholar
  251. 251.
    Lei K, Davis RJ. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA 2003; 100: 2432-2437.Google Scholar
  252. 252.
    Muchmore SW, Sattler M, Liang H, et al. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature 1996; 381: 335-341.Google Scholar
  253. 253.
    Liang H, Fesik SW. Three-dimensional structures of proteins involved in programmed cell death. J Mol Biol 1997; 274: 291-302.Google Scholar
  254. 254.
    Chang BS, Minn AJ, Muchmore SW, Fesik SW, Thompson CB. Identification of a novel regulatory domain in Bcl-X(L) and Bcl-2. EMBO J 1997; 16: 968-977.Google Scholar
  255. 255.
    Haldar S, Jena N, Croce CM. Inactivation of Bcl-2 by phosphorylation. Proc Natl Acad Sci USA 1995; 92: 4507-4511.Google Scholar
  256. 256.
    Rodi DJ, Janes RW, Sanganee HJ, et al. Screening of a library of phage-displayed peptides identifies human bcl-2 as a taxolbinding protein. J Mol Biol 1999; 285: 197-203.Google Scholar
  257. 257.
    Haldar S, Basu A, Croce CM. Bcl2 is the guardian of microtubule integrity. Cancer Res 1997; 57: 229-233.Google Scholar
  258. 258.
    Srivastava RK, Srivastava AR, Korsmeyer SJ, et al. Involvement of microtubules in the regulation of Bcl2 phosphorylation and apoptosis through cyclic AMP-dependent protein kinase. Mol Cell Biol 1998; 18: 3509-3517.Google Scholar
  259. 259.
    Basu A, Haldar S. Microtubule-damaging drugs triggered bcl2 phosphorylation-requirement of phosphorylation on both serine-70 and serine-87 residues of bcl2 protein. Int J Oncol 1998; 13: 659-664.Google Scholar
  260. 260.
    Yamamoto K, Ichijo H, Korsmeyer SJ. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 1999; 19: 8469-8478.Google Scholar
  261. 261.
    Poommipanit PB, Chen B, Oltvai ZN. Interleukin-3 induces the phosphorylation of a distinct fraction of bcl-2. J Biol Chem 1999; 274: 1033-1039.Google Scholar
  262. 262.
    Ling YH, Tornos C, Perez-Soler R. Phosphorylation of Bcl-2 is a marker of M phase events and not a determinant of apoptosis. J Biol Chem 1998; 273: 18984-18991.Google Scholar
  263. 263.
    Chen YR, Wang X, Templeton D, Davis RJ, Tan TH. The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem 1996; 271: 31929-31936.Google Scholar
  264. 264.
    Verheij M, Bose R, Lin XH, et al. Requirement for ceramideinitiated SAPK/JNK signalling in stress-induced apoptosis. Nature 1996; 380: 75-79.Google Scholar
  265. 265.
    Yang DD, Kuan CY, Whitmarsh AJ, et al. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 1997; 389: 865-870.Google Scholar
  266. 266.
    Kuan CY, Yang DD, Samanta Roy DR, et al. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 1999; 22: 667-676.Google Scholar
  267. 267.
    Gajate C, Santos-Beneit A, Modolell M, Mollinedo F. Involvement of c-Jun NH2-terminal kinase activation and c-Jun in the induction of apoptosis by the ether phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine. Mol Pharmacol 1998; 53: 602-612.Google Scholar
  268. 268.
    Gajate C, An F, Mollinedo F. Differential cytostatic and apoptotic effects of ecteinascidin-743 in cancer cells. Transcription-dependent cell cycle arrest and transcriptionindependent JNK and mitochondrial mediated apoptosis. J Biol Chem 2002; 277: 41580-41589.Google Scholar
  269. 269.
    Gajate C, An F, Mollinedo F. Rapid and selective apoptosis in human leukemic cells induced by aplidine through a Fas/CD95-and mitochondrial-mediated mechanism. Clin Cancer Res 2003; 9: 1535-1545.Google Scholar
  270. 270.
    Cheng EH, Kirsch DG, Clem RJ, et al. Conversion of Bcl-2 to a Bax-like death effector by caspases. Science 1997; 278: 1966-1968.Google Scholar
  271. 271.
    Blagosklonny MV, Chuman Y, Bergan RC, Fojo T. Mitogen-activated protein kinase pathway is dispensable for microtubule-active drug-induced Raf-1/Bcl-2 phosphorylation and apoptosis in leukemia cells. Leukemia 1999; 13: 1028-1036.Google Scholar
  272. 272.
    Gajate C, Mollinedo F. Biological activities, mechanisms of action and biomedical prospect of the antitumor ether phospholipid ET-18-OCH(3) (edelfosine), a proapoptotic agent in tumor cells. Curr Drug Metab 2002; 3: 491-525.Google Scholar
  273. 273.
    Minn AJ, Boise LH, Thompson CB. Expression of Bcl-xL and loss of p53 can cooperate to overcome a cell cycle checkpoint induced by mitotic spindle damage. Genes Dev 1996; 10: 2621-2631.Google Scholar
  274. 274.
    Yang E, Korsmeyer SJ. Molecular thanatopsis: A discourse on the BCL2 family and cell death. Blood 1996; 88: 386-401.Google Scholar
  275. 275.
    Sato T, Hanada M, Bodrug S, et al. Interactions among members of the Bcl-2 protein family analyzed with a yeast twohybrid system. Proc Natl Acad Sci USA 1994; 91: 9238-9242.Google Scholar
  276. 276.
    Yin XM, Oltvai ZN, Korsmeyer SJ. Heterodimerization with Bax is required for Bcl-2 to repress cell death. Curr Top Microbiol Immunol 1995; 194: 331-338.Google Scholar
  277. 277.
    Haldar S, Chintapalli J, Croce CM. Taxol induces bcl-2 phosphorylation and death of prostate cancer cells. Cancer Res 1996; 56: 1253-1255.Google Scholar
  278. 278.
    Deveraux QL, Reed JC. IAP family proteins-Suppressors of apoptosis. Genes Dev 1999; 13: 239-252.Google Scholar
  279. 279.
    Miller LK. An exegesis of IAPs: Salvation and surprises from BIR motifs. Trends Cell Biol 1999; 9: 323-328.Google Scholar
  280. 280.
    LaCasse EC, Baird S, Korneluk6RG, MacKenzie AE. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1998; 17: 3247-3259.Google Scholar
  281. 281.
    Tamm I, Wang Y, Sausville E, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res 1998; 58: 5315-5320.Google Scholar
  282. 282.
    Asanuma K, Moriai R, Yajima T, et al. Survivin as a radioresistance factor in pancreatic cancer. Jpn J Cancer Res 2000; 91: 1204-1209.Google Scholar
  283. 283.
    Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998; 396: 580-584.Google Scholar
  284. 284.
    Kallio MJ, Nieminen M, Eriksson JE. Human inhibitor of apoptosis protein (IAP) survivin participates in regulation of chromosome segregation and mitotic exit. FASEB J 2001; 15: 2721-2723.Google Scholar
  285. 285.
    Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 1997; 3: 917-921.Google Scholar
  286. 286.
    Reed JC, Bischoff JR. BIRinging chromosomes through cell division-and survivin' the experience. Cell 2000; 102: 545-548.Google Scholar
  287. 287.
    Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 2001; 7: 542-547.Google Scholar
  288. 288.
    Fortugno P, Wall NR, Giodini A, et al. Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function. J Cell Sci 2002; 115: 575-585.Google Scholar
  289. 289.
    Giodini A, Kallio MJ, Wall NR, et al. Regulation of microtubule stability and mitotic progression by survivin. Cancer Res 2002; 62: 2462-2467.Google Scholar
  290. 290.
    Adida C, Crotty PL, McGrath J, et al. Developmentally regulated expression of the novel cancer anti-apoptosis gene survivin in human and mouse differentiation. Am J Pathol 1998; 152: 43-49.Google Scholar
  291. 291.
    Saitoh Y, Yaginuma Y, Ishikawa M. Analysis of Bcl-2, Bax and Survivin genes in uterine cancer. Int J Oncol 1999; 15: 137-141.Google Scholar
  292. 292.
    Konno R, Yamakawa H, Utsunomiya H, et al. Expression of survivin and Bcl-2 in the normal human endometrium. Mol Hum Reprod 2000; 6: 529-534.Google Scholar
  293. 293.
    Du C, Fang M, Li Y, Li L, Wang X. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 2000; 102: 33-42.Google Scholar
  294. 294.
    Ekert PG, Silke J, Hawkins CJ, Verhagen AM, Vaux DL. DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9. J Cell Biol 2001; 152: 483-490.Google Scholar
  295. 295.
    Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 2000; 102: 43-53.Google Scholar
  296. 296.
    Lu CD, Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 1998; 58: 1808-1812.Google Scholar
  297. 297.
    Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res 1998; 58: 5071-5074.Google Scholar
  298. 298.
    Kawasaki H, Toyoda M, Shinohara H, et al. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. Cancer 2001; 91: 2026-2032.Google Scholar
  299. 299.
    Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 2000; 6: 127-134.Google Scholar
  300. 300.
    Ito T, Shiraki K, Sugimoto K, et al. Survivin promotes cell proliferation in human hepatocellular carcinoma. Hepatology 2000; 31: 1080-1085.Google Scholar
  301. 301.
    Islam A, Kageyama H, Takada N, et al. High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma. Oncogene 2000; 19: 617-623.Google Scholar
  302. 302.
    Kato J, Kuwabara Y, Mitani M, et al. Expression of survivin in esophageal cancer: Correlation with the prognosis and response to chemotherapy. Int J Cancer 2001; 95: 92-95.Google Scholar
  303. 303.
    Monzo M, Rosell R, Felip E, et al. A novel anti-apoptosis gene: Re-expression of survivin messengerRNAas a prognosis marker in non-small-cell lung cancers. J Clin Oncol 1999; 17: 2100-2104.Google Scholar
  304. 304.
    Sarela AI, Macadam RC, Farmery SM, Markham AF, Guillou PJ. Expression of the antiapoptosis gene, survivin, predicts death from recurrent colorectal carcinoma. Gut 2000; 46: 645-650.Google Scholar
  305. 305.
    Speliotes EK, Uren A, Vaux D, Horvitz HR. The survivinlike C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone. Mol Cell 2000; 6: 211-223.Google Scholar
  306. 306.
    Verdecia MA, Huang H, Dutil E, et al. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nat Struct Biol 2000; 7: 602-608.Google Scholar
  307. 307.
    Skoufias DA, Mollinari C, Lacroix FB, Margolis RL. Human survivin is a kinetochore-associated passenger protein. J Cell Biol 2000; 151: 1575-1582.Google Scholar
  308. 308.
    Uren AG, Wong L, Pakusch M, et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol 2000; 10: 1319-1328.Google Scholar
  309. 309.
    Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC. INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. Curr Biol 2001; 11: 886-890.Google Scholar
  310. 310.
    Martineau-Thuillier S, Andreassen PR, Margolis RL. Colocalization of TD-60 and INCENP throughout G2 and mitosis: Evidence for their possible interaction in signalling cytokinesis. Chromosoma 1998; 107: 461-470.Google Scholar
  311. 311.
    Terada Y, Tatsuka M, Suzuki F, et al. AIM-1: A mammalian midbody-associated protein required for cytokinesis. EMBO J 1998; 17: 667-676.Google Scholar
  312. 312.
    Adams RR, Eckley DM, Vagnarelli P, et al. Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Chromosoma 2001; 110: 65-74.Google Scholar
  313. 313.
    Mackay AM, Ainsztein AM, Eckley DM, Earnshaw WC. A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis.J Cell Biol 1998; 140: 991-1002.Google Scholar
  314. 314.
    Li F, Ackermann EJ, Bennett CF, et al. Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol 1999; 1: 461-466.Google Scholar
  315. 315.
    Chen J, Wu W, Tahir SK, et al. Down-regulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth. Neoplasia 2000; 2: 235-241.Google Scholar
  316. 316.
    O'Connor DS, Grossman D, Plescia J, et al. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc Natl Acad Sci USA 2000; 97: 13103-13107.Google Scholar
  317. 317.
    Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem 2002; 277: 3247-3257.Google Scholar
  318. 318.
    O'Connor DS, Wall NR, Porter AC, Altieri DC. A p34(cdc2) survival checkpoint in cancer. Cancer Cell 2002; 2: 43-54.Google Scholar
  319. 319.
    Wall NR, O'Connor DS, Plescia J, Pommier Y, Altieri DC. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer Res 2003; 63: 230-235.Google Scholar
  320. 320.
    Tran J, Master Z, Yu JL, et al. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proc Natl Acad Sci USA 2002; 99: 4349-4354.Google Scholar
  321. 321.
    Draetta G. Cell cycle control in eukaryotes: Molecular mechanisms of cdc2 activation. Trends Biochem Sci 1990; 15: 378-383.Google Scholar
  322. 322.
    Reddy GP. Cell cycle: Regulatory events in G1→S transition of mammalian cells. J Cell Biochem 1994; 54: 379-386.Google Scholar
  323. 323.
    Walsh S, Margolis SS, Kornbluth S. Phosphorylation of the cyclin b1 cytoplasmic retention sequence by mitogen-activated protein kinase and plx. Mol Cancer Res 2003; 1: 280-289.Google Scholar
  324. 324.
    Gorbsky GJ, Ricketts WA. Differential expression of a phosphoepitope at the kinetochores of moving chromosomes. J Cell Biol 1993; 122: 1311-1321.Google Scholar
  325. 325.
    Nicklas RB, Ward SC, Gorbsky GJ. Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint. J Cell Biol 1995; 130: 929-939.Google Scholar
  326. 326.
    Gorbsky GJ. The mitotic spindle checkpoint. Curr Biol 2001; 11: R1001-R1004.Google Scholar
  327. 327.
    Hagting A, Karlsson C, Clute P, Jackman M, Pines J. MPF localization is controlled by nuclear export. EMBO J 1998; 17: 4127-4138.Google Scholar
  328. 328.
    Chadebech P, Truchet I, Brichese L, Valette A. Up-regulation of cdc2 protein during paclitaxel-induced apoptosis. Int J Cancer 2000; 87: 779-786.Google Scholar
  329. 329.
    Ling YH, Consoli U, Tornos C, Andreeff M, Perez-Soler R. Accumulation of cyclin B1, activation of cyclin B1-dependent kinase and induction of programmed cell death in human epidermoid carcinomaKBcells treated with taxol. Int J Cancer 1998; 75: 925-932.Google Scholar
  330. 330.
    Ling YH, Yang Y, Tornos C, Singh B, Perez-Soler R. Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells. Cancer Res 1998; 58: 3633-3640.Google Scholar
  331. 331.
    Vantieghem A, Xu Y, Assefa Z, et al. Phosphorylation of Bcl-2 in G2/M phase-arrested cells following photodynamic therapy with hypericin involves a CDK1-mediated signal and delays the onset of apoptosis. J Biol Chem 2002; 277: 37718-37731.Google Scholar
  332. 332.
    Ibrado AM, Kim CN, Bhalla K. Temporal relationship of CDK1 activation and mitotic arrest to cytosolic accumulation of cytochrome C and caspase-3 activity during Taxol-induced apoptosis of human AML HL-60 cells. Leukemia 1998; 12: 1930-1936.Google Scholar
  333. 333.
    Huang TS, Shu CH, Yang WK, Whang-Peng J. Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis. Cancer Res 1997; 57: 2974-2978.Google Scholar
  334. 334.
    Barboule N, Chadebech P, Baldin V, Vidal S, Valette A. Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line. Oncogene 1997; 15: 2867-2875.Google Scholar
  335. 335.
    Yu D, Jing T, Liu B, et al. Overexpression of ErbB2 blocks Taxol-induced apoptosis by upregulation of p21Cip1, which inhibits p34Cdc2 kinase. Mol Cell 1998; 2: 581-591.Google Scholar
  336. 336.
    Lu QL, Hanby AM, Nasser Hajibagheri MA, et al. Bcl-2 protein localizes to the chromosomes of mitotic nuclei and is correlated with the cell cycle in cultured epithelial cell lines. J Cell Sci 1994; 107: 363-371.Google Scholar
  337. 337.
    Wang TH, Wang HS. p53, apoptosis and human cancers. J Formos Med Assoc 1996; 95: 509-522.Google Scholar
  338. 338.
    Murphy M, Hinman A, Levine AJ. Wild-type p53 negatively regulates the expression of a microtubule-associated protein. Genes Dev 1996; 10: 2971-2980.Google Scholar
  339. 339.
    Zhang CC, Yang JM, White E, et al. The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells. Oncogene 1998; 16: 1617-1624.Google Scholar
  340. 340.
    Blagosklonny MV, Schulte TW, Nguyen P, et al. Taxol induction of p21WAF1 and p53 requires c-raf-1. Cancer Res 1995; 55: 4623-4626.Google Scholar
  341. 341.
    Tan G, Heqing L, Jiangbo C, et al. Apoptosis induced by low-dose paclitaxel is associated with p53 upregulation in nasopharyngeal carcinoma cells. Int J Cancer 2002; 97: 168-172.Google Scholar
  342. 342.
    Ando T, Kawabe T, Ohara H, et al. Involvement of the interaction between p21 and proliferating cell nuclear antigen for the maintenance of G2/M arrest after DNA damage. J Biol Chem 2001; 276: 42971-42977.Google Scholar
  343. 343.
    Wang HG, Miyashita T, Takayama S, et al. Apoptosis regulation by interaction of Bcl-2 protein and Raf-1 kinase. Oncogene 1994; 9: 2751-2756.Google Scholar
  344. 344.
    Reed JC. Bcl-2 and the regulation of programmed cell death. J Cell Biol 1994; 124: 1-6.Google Scholar
  345. 345.
    Krajewski S, Tanaka S, Takayama S, et al. Investigation of the subcellular distribution of the bcl-2 oncoprotein: Residence in the nuclear envelope, endoplasmic reticulum, and outer mitochondrial membranes. Cancer Res 1993; 53: 4701-4714.Google Scholar
  346. 346.
    Lithgow T, van Driel R, Bertram JF, Strasser A. The protein product of the oncogene bcl-2 is a component of the nuclear envelope, the endoplasmic reticulum, and the outer mitochondrial membrane. Cell Growth Differ 1994; 5: 411-417.Google Scholar
  347. 347.
    Fernandez-Sarabia MJ, Bischoff JR. Bcl-2 associates with the ras-related protein R-ras p23. Nature 1993; 366: 274-275.Google Scholar
  348. 348.
    Rey I, Taylor-Harris P, van Erp H, Hall A. R-ras interacts with rasGAP, neurofibromin and c-raf but does not regulate cell growth or differentiation. Oncogene 1994; 9: 685-692.Google Scholar
  349. 349.
    Blagosklonny MV, Schulte T, Nguyen P, Trepel J, Neckers LM. Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway. Cancer Res 1996; 56: 1851-1854.Google Scholar
  350. 350.
    Blagosklonny MV, Giannakakou P, el-Deiry WS, et al. Raf-1/bcl-2 phosphorylation: A step from microtubule damage to cell death. Cancer Res 1997; 57: 130-135.Google Scholar
  351. 351.
    Wang HG, Takayama S, Rapp UR, Reed JC. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci USA 1996; 93: 7063-7068.Google Scholar
  352. 352.
    Lin K, Abraham KM. Targets of p56(lck) activity in immature thymoblasts: Stimulation of the Ras/Raf/MAPK pathway. Int Immunol 1997; 9: 291-306.Google Scholar
  353. 353.
    Lovric J, Moelling K. Activation of Mil/Raf protein kinases in mitotic cells. Oncogene 1996; 12: 1109-1116.Google Scholar
  354. 354.
    Horwitz SB, Shen HJ, He L, et al. The microtubuledestabilizing activity of metablastin (p19) is controlled by phosphorylation. J Biol Chem 1997; 272: 8129-8132.Google Scholar
  355. 355.
    Zhou RP, Oskarsson M, Paules RS, et al. Ability of the c-mos product to associate with and phosphorylate tubulin. Science 1991; 251: 671-675.Google Scholar
  356. 356.
    Sontag E, Nunbhakdi-Craig V, Bloom GS, Mumby MC. A novel pool of protein phosphatase 2A is associated with microtubules and is regulated during the cell cycle. J Cell Biol 1995; 128: 1131-1144.Google Scholar
  357. 357.
    Ding A, Chen B, Fuortes M, Blum E. Association of mitogen-activated protein kinases with microtubules in mouse macrophages. J Exp Med 1996; 183: 1899-1904.Google Scholar
  358. 358.
    Reszka AA, Seger R, Diltz CD, Krebs EG, Fischer EH. Association of mitogen-activated protein kinase with the microtubule cytoskeleton. Proc Natl Acad Sci USA 1995; 92: 8881-8885.Google Scholar
  359. 359.
    Mikula M, Schreiber M, Husak Z, et al. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J 2001; 20: 1952-1962.Google Scholar
  360. 360.
    Huser M, Luckett J, Chiloeches A, et al. MEK kinase activity is not necessary for Raf-1 function. EMBO J 2001; 20: 1940-1951.Google Scholar
  361. 361.
    Majewski M, Nieborowska-Skorska M, Salomoni P, et al. Activation of mitochondrial Raf-1 is involved in the antiapoptotic effects of Akt. Cancer Res 1999; 59: 2815-2819.Google Scholar
  362. 362.
    Zhong J, Troppmair J, Rapp UR. Independent control of cell survival by Raf-1 and Bcl-2 at the mitochondria. Oncogene 2001; 20: 4807-4816.Google Scholar
  363. 363.
    Chen J, Fujii K, Zhang L, Roberts T, Fu H. Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism. Proc Natl Acad Sci USA 2001; 98: 7783-7788.Google Scholar
  364. 364.
    Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogenactivated protein kinase: Conservation of a three-kinase module from yeast to human. Physiol Rev 1999; 79: 143-180.Google Scholar
  365. 365.
    Harper SJ, LoGrasso P. Signalling for survival and death in neurones: The role of stress-activated kinases, JNK and p38. Cell Signal 2001; 13: 299-310.Google Scholar
  366. 366.
    Weston CR, Lambright DG, Davis RJ. Signal transduction. MAP kinase signaling specificity. Science 2002; 296: 2345-2347.Google Scholar
  367. 367.
    Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Genet Dev 2002; 12: 14-21.Google Scholar
  368. 368.
    Nagata K, Puls A, Futter C, et al. The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3. EMBO J 1998; 17: 149-158.Google Scholar
  369. 369.
    Subbaramaiah K, Hart JC, Norton L, Dannenberg AJ. Microtubule-interfering agents stimulate the transcription of cyclooxygenase-2. Evidence for involvement of ERK1/2AND p38 mitogen-activated protein kinase pathways. J Biol Chem 2000; 275: 14838-14845.Google Scholar
  370. 370.
    Shtil AA, Mandlekar S, Yu R, et al. Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells. Oncogene 1999; 18: 377-384.Google Scholar
  371. 371.
    Wang TH, Wang HS, Ichijo H, et al. Microtubule-interfering agents activate c-Jun N-terminal kinase/stress-activated protein kinase through both Ras and apoptosis signal-regulating kinase pathways. J Biol Chem 1998; 273: 4928-4936.Google Scholar
  372. 372.
    Tchou WW, Yie TA, Tan TH, Rom WN, Tchou-Wong KM. Role of c-Jun N-terminal kinase 1 (JNK1) in cell cycle checkpoint activated by the protease inhibitor N-acetyl-leucinylleucinyl-norleucinal. Oncogene 1999; 18: 6974-6980.Google Scholar
  373. 373.
    Kim GY, Mercer SE, Ewton DZ, et al. The stress-activated protein kinases p38 alpha and JNK1 stabilize p21(Cip1) by phosphorylation. J Biol Chem 2002; 277: 29792-29802.Google Scholar
  374. 374.
    Levkau B, Koyama H, Raines EW, et al. Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: Role of a caspase cascade. Mol Cell 1998; 1: 553-563.Google Scholar
  375. 375.
    Harvey KJ, Blomquist JF, Ucker DS. Commitment and effector phases of the physiological cell death pathway elucidated with respect to Bcl-2 caspase, and cyclin-dependent kinase activities. Mol Cell Biol 1998; 18: 2912-2922.Google Scholar
  376. 376.
    Harvey KJ, Lukovic D, Ucker DS. Caspase-dependent Cdk activity is a requisite effector of apoptotic death events. J Cell Biol 2000; 148: 59-72.Google Scholar
  377. 377.
    Maundrell K, Antonsson B, Magnenat E, et al. Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stressactivated protein kinases in the presence of the constitutively active GTP-binding protein Rac1. J Biol Chem 1997; 272: 25238-25242.Google Scholar
  378. 378.
    Srivastava RK, Mi QS, Hardwick JM, Longo DL. Deletion of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis. Proc Natl Acad Sci USA 1999; 96: 3775-3780.Google Scholar
  379. 379.
    Attalla H, Westberg JA, Andersson LC, Adlercreutz H, Makela TP. 2-Methoxyestradiol-induced phosphorylation of Bcl-2: Uncoupling from JNK/SAPK activation. Biochem Biophys Res Commun 1998; 247: 616-619.Google Scholar
  380. 380.
    Best A, Ahmed S, Kozma R, Lim L. The Ras-related GTPase Rac1 binds tubulin. J Biol Chem 1996; 271: 3756-3762.Google Scholar
  381. 381.
    Lee LF, Li G, Templeton DJ, Ting JP. Paclitaxel (Taxol)-induced gene expression and cell death are both mediated by the activation of c-Jun NH2-terminal kinase (JNK/SAPK). J Biol Chem 1998; 273: 28253-28260.Google Scholar
  382. 382.
    Karin M, Liu Z, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol 1997; 9: 240-246.Google Scholar
  383. 383.
    Koistinaho J, Hicks KJ, Sagar SM. Long-term induction of c-jun mRNA and Jun protein in rabbit retinal ganglion cells following axotomy or colchicine treatment. J Neurosci Res 1993; 34: 250-255.Google Scholar
  384. 384.
    McCloskey DE, Kaufmann SH, Prestigiacomo LJ, Davidson NE. Paclitaxel induces programmed cell death in MDA-MB-468 human breast cancer cells. Clin Cancer Res 1996; 2: 847-854.Google Scholar
  385. 385.
    Shapiro PS, Vaisberg E, Hunt AJ, et al. Activation of the MKK/ERK pathway during somatic cell mitosis: Direct interactions of active ERK with kinetochores and regulation of the mitotic 3F3/2 phosphoantigen. J Cell Biol 1998; 142: 1533-1545.Google Scholar
  386. 386.
    Verlhac MH, de Pennart H, Maro B, Cobb MH, Clarke HJ. MAP kinase becomes stably activated at metaphase and is associated with microtubule-organizing centers during meiotic maturation of mouse oocytes. Dev Biol 1993; 158: 330-340.Google Scholar
  387. 387.
    Mandelkow EM, Drewes G, Biernat J, et al. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubuleassociated protein tau. FEBS Lett 1992; 314: 315-321.Google Scholar
  388. 388.
    Reszka AA, Bulinski JC, Krebs EG, Fischer EH. Mitogenactivated protein kinase/extracellular signal-regulated kinase 2 regulates cytoskeletal organization and chemotaxis via catalytic and microtubule-specific interactions. Mol Biol Cell 1997; 8: 1219-1232.Google Scholar
  389. 389.
    Morishima-Kawashima M, Kosik KS. The pool of map kinase associated with microtubules is small but constitutively active. Mol Biol Cell 1996; 7: 893-905.Google Scholar
  390. 390.
    Drewes G, Lichtenberg-Kraag B, Doring F, et al. Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer-like state. EMBO J 1992; 11: 2131-2138.Google Scholar
  391. 391.
    Hoshi M, Ohta K, Gotoh Y, et al. Mitogen-activated-proteinkinase-catalyzed phosphorylation of microtubule-associated proteins, microtubule-associated protein 2 and microtubuleassociated protein 4, induces an alteration in their function. Eur J Biochem 1992; 203: 43-52.Google Scholar
  392. 392.
    Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995; 9: 726-735.Google Scholar
  393. 393.
    Hasegawa M, Morishima-Kawashima M, Takio K, et al. Protein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain. J Biol Chem 1992; 267: 17047-17054.Google Scholar
  394. 394.
    Biernat J, Gustke N, Drewes G, Mandelkow EM, Mandelkow E. Phosphorylation of Ser262 strongly reduces binding of tau to microtubules: Distinction between PHF-like immunoreactivity and microtubule binding. Neuron 1993; 11: 153-163.Google Scholar
  395. 395.
    Lavoie JN, L'Allemain G, Brunet A, Muller R, Pouyssegur J. Cyclin D1 expression is regulated positively by the p42/p44MAPK and negatively by the p38/HOGMAPK pathway. J Biol Chem 1996; 271: 20608-20616.Google Scholar
  396. 396.
    Bitangcol JC, Chau AS, Stadnick E, et al. Activation of the p42 mitogen-activated protein kinase pathway inhibits Cdc2 activation and entry into M-phase in cycling Xenopus egg extracts. Mol Biol Cell 1998; 9: 451-467.Google Scholar
  397. 397.
    Herrera R, Hubbell S, Decker S, Petruzzelli L. A role for the MEK/MAPK pathway in PMA-induced cell cycle arrest: Modulation of megakaryocytic differentiation of K562 cells. Exp Cell Res 1998; 238: 407-414.Google Scholar
  398. 398.
    Townsend KJ, Trusty JL, Traupman MA, Eastman A, Craig RW. Expression of the antiapoptotic MCL1 gene product is regulated by a mitogen activated protein kinase-mediated pathway triggered through microtubule disruption and protein kinase C. Oncogene 1998; 17: 1223-1234.Google Scholar
  399. 399.
    Okano J, Rustgi AK. Paclitaxel induces prolonged activation of the Ras/MEK/ERK pathway independently of activating the programmed cell death machinery. J Biol Chem 2001; 276: 19555-19564.Google Scholar
  400. 400.
    McDaid HM, Horwitz SB. Selective potentiation of paclitaxel (taxol)-induced cell death by mitogen-activated protein kinase kinase inhibition in human cancer cell lines. Mol Pharmacol 2001; 60: 290-301.Google Scholar
  401. 401.
    Boldt S, Weidle UH, Kolch W. The role of MAPK pathways in the action of chemotherapeutic drugs. Carcinogenesis 2002; 23: 1831-1838.Google Scholar
  402. 402.
    MacKeigan JP, Collins TS, Ting JP. MEK inhibition enhances paclitaxel-induced tumor apoptosis. J Biol Chem 2000; 275: 38953-38956.Google Scholar
  403. 403.
    Loda M, Capodieci P, Mishra R, et al. Expression of mitogenactivated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis. Am J Pathol 1996; 149: 1553-1564.Google Scholar
  404. 404.
    Schmidt CM, McKillop IH, Cahill PA, Sitzmann JV. Increased MAPK expression and activity in primary human hepatocellular carcinoma. Biochem Biophys Res Commun 1997; 236: 54-58.Google Scholar
  405. 405.
    Takenaka K, Moriguchi T, Nishida E. Activation of the protein kinase p38 in the spindle assembly checkpoint and mitotic arrest. Science 1998; 280: 599-602.Google Scholar
  406. 406.
    Kurata S. Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress. J Biol Chem 2000; 275: 23413-23416.Google Scholar
  407. 407.
    Karin M, Lin A. NF-kappaB at the crossroads of life and death. Nat Immunol 2002; 3: 221-227.Google Scholar
  408. 408.
    Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer 2002; 2: 301-310.Google Scholar
  409. 409.
    Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 1996; 274: 782-784.Google Scholar
  410. 410.
    Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science 1996; 274: 787-789.Google Scholar
  411. 411.
    Wang CY, Mayo MW, Baldwin AS, Jr. TNF-and cancer therapy-induced apoptosis: Potentiation by inhibition of NFkappaB. Science 1996; 274: 784-787.Google Scholar
  412. 412.
    Cassimeris L. Accessory protein regulation of microtubule dynamics throughout the cell cycle. Curr Opin Cell Biol 1999; 11: 134-141.Google Scholar
  413. 413.
    Huang Y, Johnson KR, Norris JS, Fan W. Nuclear factorkappaB/ IkappaB signaling pathway may contribute to the mediation of paclitaxel-induced apoptosis in solid tumor cells. Cancer Res 2000; 60: 4426-4432.Google Scholar
  414. 414.
    Bourgarel-Rey V, Vallee S, Rimet O, et al. Involvement of nuclear factor kappaB in c-Myc induction by tubulin polymerization inhibitors. Mol Pharmacol 2001; 59: 1165-1170.Google Scholar
  415. 415.
    Patel NM, Nozaki S, Shortle NH, et al. Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappaB is enhanced by IkappaBalpha super-repressor and parthenolide. Oncogene 2000; 19: 4159-4169.Google Scholar
  416. 416.
    Downward J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 1998; 10: 262-267.Google Scholar
  417. 417.
    Franke TF, Yang SI, Chan TO, et al. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGFactivated phosphatidylinositol 3-kinase. Cell 1995; 81: 727-736.Google Scholar
  418. 418.
    Datta SR, Dudek H, Tao X, et al. Akt phosphorylation ofBAD couples survival signals to the cell-intrinsic death machinery. Cell 1997; 91: 231-241.Google Scholar
  419. 419.
    Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998; 282: 1318-1321.Google Scholar
  420. 420.
    Brunet A, Bonni A, Zigmond MJ, et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 1999; 96: 857-868.Google Scholar
  421. 421.
    Page C, Lin HJ, Jin Y, et al. Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis. Anticancer Res 2000; 20: 407-416.Google Scholar
  422. 422.
    Mitsuuchi Y, Johnson SW, Selvakumaran M, et al. The phosphatidylinositol 3-kinase/AKT signal transduction pathway plays a critical role in the expression of p21WAF1/CIP1/SDI1 induced by cisplatin and paclitaxel. Cancer Res 2000; 60: 5390-5394.Google Scholar
  423. 423.
    Kidd JF, Pilkington MF, Schell MJ, et al. Paclitaxel affects cytosolic calcium signals by opening the mitochondrial permeability transition pore. J Biol Chem 2002; 277: 6504-6510.Google Scholar
  424. 424.
    Andre N, Braguer D, Brasseur G, et al. Paclitaxel induces release of cytochrome c from mitochondria isolated from human neuroblastoma cells. Cancer Res 2000; 60: 5349-5353.Google Scholar
  425. 425.
    Andre N, Carre M, Brasseur G, et al. Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells. FEBS Lett 2002; 532: 256-260.Google Scholar
  426. 426.
    Carre M, Carles G, Andre N, et al. Involvement of microtubules and mitochondria in the antagonism of arsenic trioxide on paclitaxel-induced apoptosis. Biochem Pharmacol 2002; 63: 1831-1842.Google Scholar
  427. 427.
    Carre M, Andre N, Carles G, et al. Tubulin is an inherent component of mitochondrial membranes that interacts with the voltage-dependent anion channel. J Biol Chem 2002; 277: 33664-33669.Google Scholar
  428. 428.
    Janicke RU, Sprengart ML, Wati MR, Porter AG. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 1998; 273: 9357-9360.Google Scholar
  429. 429.
    Casazza AM, Fairchild CR. Paclitaxel (Taxol): Mechanisms of Resistance. Cancer Treat Res 1996; 87: 149-171.Google Scholar
  430. 430.
    Ling V. Charles F. Kettering Prize. P-glycoprotein and resistance to anticancer drugs. Cancer 1992; 69: 2603-2609.Google Scholar
  431. 431.
    Horwitz SB, Cohen D, Rao S, et al. Taxol: Mechanisms of action and resistance. J Natl Cancer Inst Monogr 1993; 15: 55-61.Google Scholar
  432. 432.
    Haber M, Burkhart CA, Regl DL, et al. Altered expression of M beta 2, the class II beta-tubulin isotype, in a murine J774.2 cell line with a high level of taxol resistance. J Biol Chem 1995; 270: 31269-31275.Google Scholar
  433. 433.
    Jaffrezou JP, Dumontet C, Derry WB, et al. Novel mechanism of resistance to paclitaxel (Taxol) in human K562 leukemia cells by combined selection with PSC 833. Oncol Res 1995; 7: 517-527.Google Scholar
  434. 434.
    Kavallaris M, Kuo DY, Burkhart CA, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J Clin Invest 1997; 100: 1282-1293.Google Scholar
  435. 435.
    Ranganathan S, Benetatos CA, Colarusso PJ, Dexter DW, Hudes GR. Altered beta-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells. Br J Cancer 1998; 77: 562-566.Google Scholar
  436. 436.
    Cabral F, Sobel ME, Gottesman MM. CHO mutants resistant to colchicine, colcemid or griseofulvin have an altered betatubulin. Cell 1980; 20: 29-36.Google Scholar
  437. 437.
    Ohta S, Krishan A, Nishio K, et al. Effect of taxol on vinblastine sulfate-induced crystallization of tubulin. Anticancer Res 1993; 13: 873-877.Google Scholar
  438. 438.
    Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: Microtubule dynamics, drug transport, and cell death. J Clin Oncol 1999; 17: 1061-1070.Google Scholar
  439. 439.
    Gonzalez-Garay ML, Chang L, Blade K, Menick DR, Cabral F. A beta-tubulin leucine cluster involved in microtubule assembly and paclitaxel resistance. J Biol Chem 1999; 274: 23875-23882.Google Scholar
  440. 440.
    Jordan A, Thrower D, Wilson L. Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 1991; 51: 2212-2222.Google Scholar
  441. 441.
    Lieu CH, Chang YN, Lai YK. Dual cytotoxic mechanisms of submicromolar taxol on human leukemia HL-60 cells. Biochem Pharmacol 1997; 53: 1587-1596.Google Scholar
  442. 442.
    Trielli MO, Andreassen PR, Lacroix FB, Margolis RL. Differential Taxol-dependent arrest of transformed and nontransformed cells in the G1 phase of the cell cycle, and specificrelated mortality of transformed cells. J Cell Biol 1996; 135: 689-700.Google Scholar
  443. 443.
    Jordan MA, Toso RJ, Thrower D, Wilson L. Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci USA 1993; 90: 9552-9556.Google Scholar
  444. 444.
    Minshull J, Straight A, Rudner AD, et al. Protein phosphatase 2A regulates MPF activity and sister chromatid cohesion in budding yeast. Curr Biol 1996; 6: 1609-1620.Google Scholar
  445. 445.
    Lieu CH, Liu CC, Yu TH, et al. Role of mitogen-activated protein kinase in taxol-induced apoptosis in human leukemic U937 cells. Cell Growth Differ 1998; 9: 767-776.Google Scholar
  446. 446.
    Roth W, Wagenknecht B, Grimmel C, Dichgans J, Weller M. Taxol-mediated augmentation of CD95 ligand-induced apoptosis of human malignant glioma cells: Association with bcl-2 phosphorylation but neither activation of p53 nor G2/M cell cycle arrest. Br J Cancer 1998; 77: 404-411.Google Scholar
  447. 447.
    Haldar S, Basu A, Croce CM. Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells. Cancer Res 1998; 58: 1609-1615.Google Scholar
  448. 448.
    Tsukidate K, Yamamoto K, Snyder JW, Farber JL. Microtubule antagonists activate programmed cell death (apoptosis) in cultured rat hepatocytes. Am J Pathol 1993; 143: 918-925.Google Scholar
  449. 449.
    Jones NA, Turner J, McIlwrath AJ, Brown R, Dive C. Cisplatin-and paclitaxel-induced apoptosis of ovarian carcinoma cells and the relationship between bax and bak upregulation and the functional status of p53. Mol Pharmacol 1998; 53: 819-826.Google Scholar
  450. 450.
    Moos PJ, Fitzpatrick FA. Taxane-mediated gene induction is independent of microtubule stabilization: Induction of transcription regulators and enzymes that modulate inflammation and apoptosis. Proc Natl Acad Sci USA 1998; 95: 3896-3901.Google Scholar
  451. 451.
    Manthey CL, Brandes ME, Perera PY, Vogel SN. Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages. J Immunol 1992; 149: 2459-2465.Google Scholar
  452. 452.
    Shibuya EK, Ruderman JV. Mos induces the in vitro activation of mitogen-activated protein kinases in lysates of frog oocytes and mammalian somatic cells. Mol Biol Cell 1993; 4: 781-790.Google Scholar
  453. 453.
    Daar I, Paules RS, Vande Woude GF. A characterization of cytostatic factor activity from Xenopus eggs and c-mostransformed cells. J Cell Biol 1991; 114: 329-335.Google Scholar
  454. 454.
    Sagata N, Watanabe N, VandeWoude GF, Ikawa Y. The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs. Nature 1989; 342: 512-518.Google Scholar
  455. 455.
    Gao C, Arlinghaus RB, Singh B. Further characterization of the c-mos transcript and its cell cycle specific expression in NIH3T3 cells. Oncogene 1996; 12: 1571-1576.Google Scholar
  456. 456.
    Zhou R, Daar I, Ferris DK, et al. pp39mos is associated with p34cdc2 kinase in c-mosxe-transformed NIH 3T3 cells. Mol Cell Biol 1992; 12: 3583-3589.Google Scholar
  457. 457.
    Wang XM, Yew N, Peloquin JG, Vande Woude GF, Borisy GG. Mos oncogene product associates with kinetochores in mammalian somatic cells and disrupts mitotic progression. Proc Natl Acad Sci USA 1994; 91: 8329-8333.Google Scholar
  458. 458.
    Fukasawa K, Rulong S, Resau J, Pinto da Silva P, Woude GF. Overexpression of mos oncogene product in Swiss 3T3 cells induces apoptosis preferentially during S-phase. Oncogene 1995; 10: 1-8.Google Scholar
  459. 459.
    O'Keefe SJ, Kiessling AA, Cooper GM. The c-mos gene product is required for cyclin B accumulation during meiosis of mouse eggs. Proc Natl Acad Sci USA 1991; 88: 7869-7872.Google Scholar
  460. 460.
    Fan W. Possible mechanisms of paclitaxel-induced apoptosis. Biochem Pharmacol 1999; 57: 1215-1221.Google Scholar
  461. 461.
    Huang TS, Shu CH, Chao Y, Chen SN, Chen LL. Activation of MAD 2 checkprotein and persistence of cyclin B1/CDC 2 activity associate with paclitaxel-induced apoptosis in human nasopharyngeal carcinoma cells. Apoptosis 2000; 5: 235-241.Google Scholar
  462. 462.
    Rieder CL, Cole R. Microtubule disassembly delays the G2-M transition in vertebrates. Curr Biol 2000; 10: 1067-1070.Google Scholar
  463. 463.
    Blajeski AL, Phan VA, Kottke TJ, Kaufmann SH. G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells. J Clin Invest 2002; 110: 91-99.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • F. Mollinedo
    • 1
  • C. Gajate
    • 1
  1. 1.Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del CáncerConsejo Superior de Investigaciones Científicas-Universidad de Salamanca, Campus Miguel de UnamunoSalamancaSpain

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