Epigenic modifications, mainly DNA methylation and acetylation, are recognized as the main mechanisms contributing to the malignant phenotype. Acetylation and deacetylation are catalyzed by specific enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. While histones represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcriptionindependent mechanisms by modulating the acetylation status of a series of nonhistone proteins. HDAC inhibitors may act through the transcriptional reactivation of dormant tumor suppressor genes. They also modulate expression of several other genes related to cell cycle, apoptosis, and angiogenesis. Several HDAC inhibitors are currently in clinical trials both for solid and hematologic malignancies. Thus, HDAC inhibitors, in combination with DNA-demethylating agents, chemopreventive, or classical chemotherapeutic drugs, could be promising candidates for cancer therapy. Here, we review the molecular mechanisms and therapeutic potential of HDAC inhibitors for the treatment of cancer.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Acharya, M. R. and Figg, W. D. (2004). Histone deacetylase inhibitor enhances the anti-leukemic activity of an established nucleoside analogue. Cancer Biol Ther 3, 719–720.
Allen, L. E. and Maher, P. A. (1993). Expression of basic fibroblast growth factor and its receptor in an invasive bladder carcinoma cell line. J Cell Physiol 155, 368–375.
Amin, H. M., Saeed, S., and Alkan, S. (2001). Histone deacetylase inhibitors induce caspase-dependent apoptosis and downregulation of daxx in acute promyelocytic leukaemia with t(15;17). Br J Haematol 115, 287–297.
Appelskog, I. B., Ammerpohl, O., Svechnikova, I. G., Lui, W. O., Almqvist, P. M., and Ekstrom, T. J. (2004). Histone deacetylase inhibitor 4-phenylbutyrate suppresses GAPDH mRNA expression in glioma cells. Int J Oncol 24, 1419–1425.
Archer, S. Y., Meng, S., Shei, A., and Hodin, R. A. (1998). p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. Proc Natl Acad Sci USA 95, 6791–6796.
Aron, J. L., Parthun, M. R., Marcucci, G., Kitada, S., Mone, A. P., Davis, M. E., Shen, T., Murphy, T., Wickham, J., Kanakry, C., et al. (2003). Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase-8-mediated apoptosis and down-regulation of c-FLIP protein. Blood 102, 652–658.
Bali, P., George, P., Cohen, P., Tao, J., Guo, F., Sigua, C., Vishvanath, A., Scuto, A., Annavarapu, S., Fiskus, W., et al. (2004). Superior activity of the combination of histone deacetylase inhibitor LAQ824 and the FLT-3 kinase inhibitor PKC412 against human acute myelogenous leukemia cells with mutant FLT-3. Clin Cancer Res 10, 4991–4997.
Bandyopadhyay, D., Mishra, A., and Medrano, E. E. (2004). Overexpression of histone deacetylase 1 confers resistance to sodium butyrate-mediated apoptosis in melanoma cells through a p53-mediated pathway. Cancer Res 64, 7706–7710.
Bapna, A., Vickerstaffe, E., Warrington, B. H., Ladlow, M., Fan, T. P., and Ley, S. V. (2004). Polymer-assisted, multi-step solution phase synthesis and biological screening of histone deacetylase inhibitors. Org Biomol Chem 2, 611–620.
Baylin, S. and Bestor, T. H. (2002). Altered methylation patterns in cancer cell genomes: cause or consequence? Cancer Cell 1, 299–305.
Baylin, S. B., Esteller, M., Rountree, M. R., Bachman, K. E., Schuebel, K., and Herman, J. G. (2001). Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet 10, 687–692.
Bevins, R. L. and Zimmer, S. G. (2005). It’s about time: scheduling alters effect of histone deacetylase inhibitors on camptothecin-treated cells. Cancer Res 65, 6957–6966.
Blagosklonny, M. V., Robey, R., Bates, S., and Fojo, T. (2000). Pretreatment with DNA-damaging agents permits selective killing of checkpoint-deficient cells by microtubule-active drugs. J Clin Invest 105, 533–539.
Blanchard, F. and Chipoy, C. (2005). Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? Drug Discov Today 10, 197–204.
Boivin, A. J., Momparler, L. F., Hurtubise, A., and Momparler, R. L. (2002). Antineoplastic action of 5-aza-2z-deoxycytidine and phenylbutyrate on human lung carcinoma cells. Anticancer Drugs 13, 869–874.
Bordin, M., D’Atri, F., Guillemot, L., and Citi, S. (2004). Histone deacetylase inhibitors up-regulate the expression of tight junction proteins. Mol Cancer Res 2, 692–701.
Bordone, L. and Guarente, L. (2005). Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 6, 298–305.
Bouillet, P., Purton, J. F., Godfrey, D. I., Zhang, L. C., Coultas, L., Puthalakath, H., Pellegrini, M., Cory, S., Adams, J. M., and Strasser, A. (2002). BH3-only Bcl-2 family member Bim is required for apoptosis of autoreactive thymocytes. Nature 415, 922–926.
Bouillet, P. and Strasser, A. (2002). BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci 115, 1567–1574.
Bouras, T., Fu, M., Sauve, A. A., Wang, F., Quong, A. A., Perkins, N. D., Hay, R. T., Gu, W., and Pestell, R. G. (2005). SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem 280, 10264–10276.
Boyle, G. M., Martyn, A. C., and Parsons, P. G. (2005). Histone deacetylase inhibitors and malignant melanoma. Pigment Cell Res 18, 160–166.
Bradbury, C. A., Khanim, F. L., Hayden, R., Bunce, C. M., White, D. A., Drayson, M. T., Craddock, C., and Turner, B. M. (2005). Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia 19, 1751–1759.
Braunstein, M., Rose, A. B., Holmes, S. G., Allis, C. D., and Broach, J. R. (1993). Transcriptional silencing in yeast is associated with reduced nucleosome acetylation. Genes Dev 7, 592–604.
Brosch, G., Ransom, R., Lechner, T., Walton, J. D., and Loidl, P. (1995). Inhibition of maize histone deacetylases by HC toxin, the host-selective toxin of Cochliobolus carbonum. Plant Cell 7, 1941–1950.
Brown, L. F., Berse, B., Jackman, R. W., Tognazzi, K., Manseau, E. J., Dvorak, H. F., and Senger, D. R. (1993a). Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143, 1255–1262.
Brown, L. F., Berse, B., Jackman, R. W., Tognazzi, K., Manseau, E. J., Senger, D. R., and Dvorak, H. F. (1993b). Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in adenocarcinomas of the gastrointestinal tract. Cancer Res 53, 4727–4735.
Brush, M. H., Guardiola, A., Connor, J. H., Yao, T. P., and Shenolikar, S. (2004). Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases. J Biol Chem 279, 7685–7691.
Butler, L. M., Agus, D. B., Scher, H. I., Higgins, B., Rose, A., Cordon-Cardo, C., Thaler, H. T., Rifkind, R. A., Marks, P. A., and Richon, V. M. (2000). Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res 60, 5165–5170.
Byrd, J. C., Marcucci, G., Parthun, M. R., Xiao, J. J., Klisovic, R. B., Moran, M., Lin, T. S., Liu, S., Sklenar, A. R., Davis, M. E., et al. (2005). A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia. Blood 105, 959–967.
Camphausen, K., Burgan, W., Cerra, M., Oswald, K. A., Trepel, J. B., Lee, M. J., and Tofilon, P. J. (2004). Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275. Cancer Res 64, 316–321.
Camphausen, K., Cerna, D., Scott, T., Sproull, M., Burgan, W. E., Cerra, M. A., Fine, H., and Tofilon, P. J. (2005). Enhancement of in vitro and in vivo tumor cell radiosensitivity by valproic acid. Int J Cancer 114, 380–386.
Canes, D., Chiang, G. J., Billmeyer, B. R., Austin, C. A., Kosakowski, M., Rieger-Christ, K. M., Libertino, J. A., and Summerhayes, I. C. (2005). Histone deacetylase inhibitors upregulate plakoglobin expression in bladder carcinoma cells and display antineoplastic activity in vitro and in vivo. Int J Cancer 113, 841–848.
Canettieri, G., Morantte, I., Guzman, E., Asahara, H., Herzig, S., Anderson, S. D., Yates, J. R., III, and Montminy, M. (2003). Attenuation of a phosphorylation-dependent activator by an HDAC-PP1 complex. Nat Struct Biol 10, 175–181.
Caponigro, F., Basile, M., de Rosa, V., and Normanno, N. (2005). New drugs in cancer therapy, National Tumor Institute, Naples, 17–18 June 2004. Anticancer Drugs 16, 211–221.
Cassidy, A., Bingham, S. A., and Cummings, J. H. (1994). Starch intake and colorectal cancer risk: an international comparison. Br J Cancer 69, 937–942.
Catalano, M. G., Fortunati, N., Pugliese, M., Costantino, L., Poli, R., Bosco, O., and Boccuzzi, G. (2005). Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells. J Clin Endocrinol Metab 90, 1383–1389.
Chen, C. S., Weng, S. C., Tseng, P. H., Lin, H. P., and Chen, C. S. (2005). Histone acetylation-independent effect of histone deacetylase inhibitors on akt through the reshuffling of protein phosphatase 1 complexes. J Biol Chem 280, 38879–38887.
Chen, W. Y., Bailey, E. C., McCune, S. L., Dong, J. Y., and Townes, T. M. (1997). Reactivation of silenced, virally transduced genes by inhibitors of histone deacetylase. Proc Natl Acad Sci USA 94, 5798–5803.
Chen, X., Kandasamy, K., and Srivastava, R. K. (2003). Differential roles of RelA (p65) and c-Rel subunits of nuclear factor kappa B in tumor necrosis factor-related apoptosis-inducing ligand signaling. Cancer Res 63, 1059–1066.
Cheong, J. W., Chong, S. Y., Kim, J. Y., Eom, J. I., Jeung, H. K., Maeng, H. Y., Lee, S. T., and Min, Y. H. (2003). Induction of apoptosis by apicidin, a histone deacetylase inhibitor, via the activation of mitochondria-dependent caspase cascades in human Bcr-Abl-positive leukemia cells. Clin Cancer Res 9, 5018–5027.
Chinnaiyan, A. M., Prasad, U., Shankar, S., Hamstra, D. A., Shanaiah, M., Chenevert, T. L., Ross, B. D., and Rehemtulla, A. (2000). Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proc Natl Acad Sci USA 97, 1754–1759.
Chinnaiyan, P., Vallabhaneni, G., Armstrong, E., Huang, S. M., and Harari, P. M. (2005a). Modulation of radiation response by histone deacetylase inhibition. Int J Radiat Oncol Biol Phys 62, 223–229.
Chinnaiyan, P., Varambally, S., Tomlins, S. A., Ray, S., Huang, S., Chinnaiyan, A. M., and Harari, P. M. (2005b). Enhancing the antitumor activity of ErbB blockade with histone deacetylase (HDAC) inhibition. Int. J. Cancer 118(4), 1041–1050.
Chobanian, N. H., Greenberg, V. L., Gass, J. M., Desimone, C. P., Van Nagell, J. R., and Zimmer, S. G. (2004). Histone deacetylase inhibitors enhance paclitaxel-induced cell death in ovarian cancer cell lines independent of p53 status. Anticancer Res 24, 539–545.
Choi, J. H., Oh, S. W., Kang, M. S., Kwon, H. J., Oh, G. T., and Kim, D. Y. (2005). Trichostatin A attenuates airway inflammation in mouse asthma model. Clin Exp Allergy 35, 89–96.
Cohen, H. Y., Lavu, S., Bitterman, K. J., Hekking, B., Imahiyerobo, T. A., Miller, C., Frye, R., Ploegh, H., Kessler, B. M., and Sinclair, D. A. (2004a). Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol Cell 13, 627–638.
Cohen, H. Y., Miller, C., Bitterman, K. J., Wall, N. R., Hekking, B., Kessler, B., Howitz, K. T., Gorospe, M., de Cabo, R., and Sinclair, D. A. (2004b). Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305, 390–392.
Cohen, L. A., Amin, S., Marks, P. A., Rifkind, R. A., Desai, D., and Richon, V. M. (1999). Chemoprevention of carcinogen-induced mammary tumorigenesis by the hybrid polar cytodifferentiation agent, suberanilohydroxamic acid (SAHA). Anticancer Res 19, 4999–5005.
Darkin-Rattray, S. J., Gurnett, A. M., Myers, R. W., Dulski, P. M., Crumley, T. M., Allocco, J. J., Cannova, C., Meinke, P. T., Colletti, S. L., Bednarek, M. A., et al. (1996). Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci USA 93, 13143–13147.
De Felice, L., Tatarelli, C., Mascolo, M. G., Gregorj, C., Agostini, F., Fiorini, R., Gelmetti, V., Pascale, S., Padula, F., Petrucci, M. T., et al. (2005). Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res 65, 1505–1513.
de Haan, J. B., Gevers, W., and Parker, M. I. (1986). Effects of sodium butyrate on the synthesis and methylation of DNA in normal cells and their transformed counterparts. Cancer Res 46, 713–716.
de Ruijter, A. J., van Gennip, A. H., Caron, H. N., Kemp, S., and van Kuilenburg, A. B. (2003). Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J 370, 737–749.
Debatin, K. M. and Krammer, P. H. (2004). Death receptors in chemotherapy and cancer. Oncogene 23, 2950–2966.
Degenhardt, K., Chen, G., Lindsten, T., and White, E. (2002a). BAX and BAK mediate p53-independent suppression of tumorigenesis. Cancer Cell 2, 193–203.
Degenhardt, K., Sundararajan, R., Lindsten, T., Thompson, C., and White, E. (2002b). Bax and Bak independently promote cytochrome C release from mitochondria. J Biol Chem 277, 14127–14134.
Dehm, S. M. and Bonham, K. (2004). SRC gene expression in human cancer: the role of transcriptional activation. Biochem. Cell Biol 82, 263–274.
Deroanne, C. F., Bonjean, K., Servotte, S., Devy, L., Colige, A., Clausse, N., Blacher, S., Verdin, E., Foidart, J. M., Nusgens, B. V., and Castronovo, V. (2002). Histone deacetylases inhibitors as anti-angiogenic agents altering vascular endothelial growth factor signaling. Oncogene 21, 427–436.
Deveraux, Q. L. and Reed, J. C. (1999). IAP family proteins–suppressors of apoptosis. Genes Dev 13, 239–252.
Deveraux, Q. L., Stennicke, H. R., Salvesen, G. S., and Reed, J. C. (1999). Endogenous inhibitors of caspases. J Clin Immunol 19, 388–398.
Doi, S., Soda, H., Oka, M., Tsurutani, J., Kitazaki, T., Nakamura, Y., Fukuda, M., Yamada, Y., Kamihira, S., and Kohno, S. (2004). The histone deacetylase inhibitor FR901228 induces caspase-dependent apoptosis via the mitochondrial pathway in small cell lung cancer cells. Mol Cancer Ther 3, 1397–1402.
Donadelli, M., Costanzo, C., Faggioli, L., Scupoli, M. T., Moore, P. S., Bassi, C., Scarpa, A., and Palmieri, M. (2003). Trichostatin A, an inhibitor of histone deacetylases, strongly suppresses growth of pancreatic adenocarcinoma cells. Mol Carcinog 38, 59–69.
Druesne, N., Pagniez, A., Mayeur, C., Thomas, M., Cherbuy, C., Duee, P. H., Martel, P., and Chaumontet, C. (2004). Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1) expression in human colon tumor cell lines. Carcinogenesis 25, 1227–1236.
Du, C., Fang, M., Li, Y., Li, L., and Wang, X. (2000). Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33–42.
Duan, H., Heckman, C. A., and Boxer, L. M. (2005). Histone deacetylase inhibitors down-regulate bcl-2 expression and induce apoptosis in t(14;18) lymphomas. Mol Cell Biol 25, 1608–1619.
Emiliani, S., Fischle, W., Van Lint, C., Al-Abed, Y., and Verdin, E. (1998). Characterization of a human RPD3 ortholog, HDAC3. Proc Natl Acad Sci USA 95, 2795–2800.
Facchetti, F., Previdi, S., Ballarini, M., Minucci, S., Perego, P., and La Porta, C. A. (2004). Modulation of pro- and anti-apoptotic factors in human melanoma cells exposed to histone deacetylase inhibitors. Apoptosis 9, 573–582.
Fandy, T. E. and Srivastava, R. K. (2006). Trichostatin A sensitizes TRAIL-resistant myeloma cells by downregulation of the antiapoptotic Bcl-2 proteins. Cancer Chemother Pharmacol 58, 471–477.
Fandy, T. E., Shankar, S., Ross, D. D., Sausville, E., and Srivastava, R. K. (2005). Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma. Neoplasia 7, 646–657.
Fang, J. Y. (2005). Histone deacetylase inhibitors, anticancerous mechanism and therapy for gastrointestinal cancers. J Gastroenterol Hepatol 20, 988–994.
Fenic, I., Sonnack, V., Failing, K., Bergmann, M., and Steger, K. (2004). In vivo effects of histone-deacetylase inhibitor trichostatin-A on murine spermatogenesis. J Androl 25, 811–818.
Fischle, W., Emiliani, S., Hendzel, M. J., Nagase, T., Nomura, N., Voelter, W., and Verdin, E. (1999). A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p. J Biol Chem 274, 11713–11720.
Folkman, J. (2002). Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29, 15–18.
Folkman, J. (2003a). Angiogenesis and apoptosis. Semin Cancer Biol 13, 159–167.
Folkman, J. (2003b). Angiogenesis and proteins of the hemostatic system. J Thromb Haemost 1, 1681–1682.
Folkman, J. (2003c). Antiangiogenic activity of a matrix protein. Cancer Biol Ther 2, 53–54.
Folkman, J. (2003d). Fundamental concepts of the angiogenic process. Curr Mol Med 3, 643–651.
Folkman, J. and Kalluri, R. (2004). Cancer without disease. Nature 427, 787.
Ford, J., Jiang, M., and Milner, J. (2005). Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival. Cancer Res 65, 10457–10463.
Fronsdal, K. and Saatcioglu, F. (2005). Histone deacetylase inhibitors differentially mediate apoptosis in prostate cancer cells. Prostate 62, 299–306.
Frye, R. A. (1999). Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun 260, 273–279.
Fu, M., Rao, M., Wang, C., Sakamaki, T., Wang, J., Di Vizio, D., Zhang, X., Albanese, C., Balk, S., Chang, C., et al. (2003). Acetylation of androgen receptor enhances coactivator binding and promotes prostate cancer cell growth. Mol Cell Biol 23, 8563–8575.
Fuino, L., Bali, P., Wittmann, S., Donapaty, S., Guo, F., Yamaguchi, H., Wang, H. G., Atadja, P., and Bhalla, K. (2003). Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther 2, 971–984.
Gan, Y., Shen, Y. H., Wang, J., Wang, X., Utama, B., Wang, J., and Wang, X. L. (2005). Role of histone deacetylation in cell-specific expression of endothelial nitric-oxide synthase. J Biol Chem 280, 16467–16475.
Gao, L., Cueto, M. A., Asselbergs, F., and Atadja, P. (2002). Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem 277, 25748–25755.
Gaughan, L., Logan, I. R., Cook, S., Neal, D. E., and Robson, C. N. (2002). Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. J Biol Chem 277, 25904–25913.
Gaughan, L., Logan, I. R., Neal, D. E., and Robson, C. N. (2005). Regulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation. Nucleic Acids Res 33, 13–26.
George, P., Bali, P., Annavarapu, S., Scuto, A., Fiskus, W., Guo, F., Sigua, C., Sondarva, G., Moscinski, L., Atadja, P., and Bhalla, K. (2005). Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3. Blood 105, 1768–1776.
Glass, C. K. and Rosenfeld, M. G. (2000). The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14, 121–141.
Goldsmith, K. C. and Hogarty, M. D. (2005). Targeting programmed cell death pathways with experimental therapeutics: opportunities in high-risk neuroblastoma. Cancer Lett 228, 133–141.
Gozzini, A. and Santini, V. (2005). Butyrates and decitabine cooperate to induce histone acetylation and granulocytic maturation of t(8;21) acute myeloid leukemia blasts. Ann Hematol 1–7.
Gray, S. G. and Ekstrom, T. J. (2001). The human histone deacetylase family. Exp Cell Res 262, 75–83.
Green, D. R. and Reed, J. C. (1998). Mitochondria and apoptosis. Science 281, 1309–1312.
Greene, W. C. and Chen, L. F. (2004). Regulation of NF-kappaB action by reversible acetylation. Novartis Found. Symp 259, 208–217; discussion 218–225.
Grignani, F., De Matteis, S., Nervi, C., Tomassoni, L., Gelmetti, V., Cioce, M., Fanelli, M., Ruthardt, M., Ferrara, F. F., Zamir, I., et al. (1998). Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature 391, 815–818.
Grimm, S., Bauer, M. K., Baeuerle, P. A., and Schulze-Osthoff, K. (1996). Bcl-2 down-regulates the activity of transcription factor NF-kappaB induced upon apoptosis. J Cell Biol 134, 13–23.
Gross, A. (2001). BCL-2 proteins: regulators of the mitochondrial apoptotic program. IUBMB Life 52, 231–236.
Gross, A., McDonnell, J. M., and Korsmeyer, S. J. (1999). BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13, 1899–1911.
Grozinger, C. M. and Schreiber, S. L. (2000). Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14–3-3-dependent cellular localization. Proc Natl Acad Sci USA 97, 7835–7840.
Grozinger, C. M., Hassig, C. A., and Schreiber, S. L. (1999). Three proteins define a class of human histone deacetylases related to yeast Hda1p. Proc Natl Acad Sci USA 96, 4868–4873.
Grunstein, M. (1997). Histone acetylation in chromatin structure and transcription. Nature 389, 349–352.
Han, J. W., Ahn, S. H., Park, S. H., Wang, S. Y., Bae, G. U., Seo, D. W., Kwon, H. K., Hong, S., Lee, H. Y., Lee, Y. W., and Lee, H. W. (2000). Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via induction of p21WAF1/Cip1 and gelsolin. Cancer Res 60, 6068–6074.
Han, J. W., Ahn, S. H., Kim, Y. K., Bae, G. U., Yoon, J. W., Hong, S., Lee, H. Y., Lee, Y. W., and Lee, H. W. (2001). Activation of p21(WAF1/Cip1) transcription through Sp1 sites by histone deacetylase inhibitor apicidin: involvement of protein kinase C. J Biol Chem 276, 42084–42090.
He, G. H., Helbing, C. C., Wagner, M. J., Sensen, C. W., and Riabowol, K. (2005). Phylogenetic analysis of the ING family of PHD finger proteins. Mol Biol Evol 22, 104–116.
Henderson, C. and Brancolini, C. (2003). Apoptotic pathways activated by histone deacetylase inhibitors: implications for the drug-resistant phenotype. Drug Resist Updat 6, 247–256.
Heruth, D. P., Zirnstein, G. W., Bradley, J. F., and Rothberg, P. G. (1993). Sodium butyrate causes an increase in the block to transcriptional elongation in the c-myc gene in SW837 rectal carcinoma cells. J Biol Chem 268, 20466–20472.
Hess-Stumpp, H. (2005). Histone deacetylase inhibitors and cancer: from cell biology to the clinic. Eur J Cell Biol 84, 109–121.
Hitomi, T., Matsuzaki, Y., Yokota, T., Takaoka, Y., and Sakai, T. (2003). p15(INK4b) in HDAC inhibitor-induced growth arrest. FEBS Lett 554, 347–350.
Hoffmann, K., Brosch, G., Loidl, P., and Jung, M. (2000). First non-radioactive assay for in vitro screening of histone deacetylase inhibitors. Pharmazie 55, 601–606.
Hong, J., Ishihara, K., Yamaki, K., Hiraizumi, K., Ohno, T., Ahn, J. W., Zee, O., and Ohuchi, K. (2003). Apicidin, a histone deacetylase inhibitor, induces differentiation of HL-60 cells. Cancer Lett 189, 197–206.
Hook, S. S., Orian, A., Cowley, S. M., and Eisenman, R. N. (2002). Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes. Proc Natl Acad Sci USA 99, 13425–13430.
Howe, G. R., Benito, E., Castelleto, R., Cornee, J., Esteve, J., Gallagher, R. P., Iscovich, J. M., Deng-ao, J., Kaaks, R., Kune, G. A., et al. (1992). Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies. J Natl Cancer Inst 84, 1887–1896.
Hu, J. and Colburn, N. H. (2005). Histone deacetylase inhibition down-regulates cyclin D1 transcription by inhibiting nuclear factor-kappaB/p65 DNA binding. Mol Cancer Res 3, 100–109.
Hylla, S., Gostner, A., Dusel, G., Anger, H., Bartram, H. P., Christl, S. U., Kasper, H., and Scheppach, W. (1998). Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention. Am J Clin Nutr 67, 136–142.
Imai, S., Armstrong, C. M., Kaeberlein, M., and Guarente, L. (2000). Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795–800.
Imai, T., Adachi, S., Nishijo, K., Ohgushi, M., Okada, M., Yasumi, T., Watanabe, K., Nishikomori, R., Nakayama, T., Yonehara, S., et al. (2003). FR901228 induces tumor regression associated with induction of Fas ligand and activation of Fas signaling in human osteosarcoma cells. Oncogene 22, 9231–9242.
Inoue, H., Shiraki, K., Ohmori, S., Sakai, T., Deguchi, M., Yamanaka, T., Okano, H., and Nakano, T. (2002). Histone deacetylase inhibitors sensitize human colonic adenocarcinoma cell lines to TNF-related apoptosis inducing ligand-mediated apoptosis. Int J Mol Med 9, 521–525.
Inoue, S., MacFarlane, M., Harper, N., Wheat, L. M., Dyer, M. J., and Cohen, G. M. (2004). Histone deacetylase inhibitors potentiate TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in lymphoid malignancies. Cell Death Differ 11 (Suppl 2), S193–S206.
Insinga, A., Minucci, S., and Pelicci, P. G. (2005a). Mechanisms of selective anticancer action of histone deacetylase inhibitors. Cell Cycle 4, 741–743.
Insinga, A., Monestiroli, S., Ronzoni, S., Gelmetti, V., Marchesi, F., Viale, A., Altucci, L., Nervi, C., Minucci, S., and Pelicci, P. G. (2005b). Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway. Nat Med 11, 71–76.
Janne, P. A. and Mayer, R. J. (2000). Chemoprevention of colorectal cancer. N Engl J Med 342, 1960–1968.
Jee, C. D., Lee, H. S., Bae, S. I., Yang, H. K., Lee, Y. M., Rho, M. S., and Kim, W. H. (2005). Loss of caspase-1 gene expression in human gastric carcinomas and cell lines. Int J Oncol 26, 1265–1271.
Jiang, Y., Ahn, E. Y., Ryu, S. H., Kim, D. K., Park, J. S., Yoon, H. J., You, S., Lee, B. J., Lee, D. S., and Jung, J. H. (2004). Cytotoxicity of psammaplin A from a two-sponge association may correlate with the inhibition of DNA replication. BMC Cancer 4, 70.
Johnson, J., Hunter, R., McElveen, R., Qian, X. H., Baliga, B. S., and Pace, B. S. (2005). Fetal hemoglobin induction by the histone deacetylase inhibitor, scriptaid. Cell Mol Biol (Noisy-le-grand) 51, 229–238.
Johnstone, R. W. (2002). Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov 1, 287–299.
Johnstone, R. W. and Licht, J. D. (2003). Histone deacetylase inhibitors in cancer therapy: is transcription the primary target? Cancer Cell 4, 13–18.
Johnstone, R. W., Ruefli, A. A., and Lowe, S. W. (2002). Apoptosis: a link between cancer genetics and chemotherapy. Cell 108, 153–164.
Jones, P. A. (2002). DNA methylation and cancer. Oncogene 21, 5358–5360.
Juan, L. J., Shia, W. J., Chen, M. H., Yang, W. M., Seto, E., Lin, Y. S., and Wu, C. W. (2000). Histone deacetylases specifically down-regulate p53-dependent gene activation. J Biol Chem 275, 20436–20443.
Jung, J. H., Sim, C. J., and Lee, C. O. (1995). Cytotoxic compounds from a two-sponge association. J Nat Prod 58, 1722–1726.
Jung, M., Brosch, G., Kolle, D., Scherf, H., Gerhauser, C., and Loidl, P. (1999). Amide analogues of trichostatin A as inhibitors of histone deacetylase and inducers of terminal cell differentiation. J Med Chem 42, 4669–4679.
Kaeberlein, M., McVey, M., and Guarente, L. (1999). The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13, 2570–2580.
Kandasamy, K., Srinivasula, S. M., Alnemri, E. S., Thompson, C. B., Korsmeyer, S. J., Bryant, J. L., and Srivastava, R. K. (2003). Involvement of proapoptotic molecules Bax and Bak in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced mitochondrial disruption and apoptosis: differential regulation of cytochrome c and Smac/DIABLO release. Cancer Res 63, 1712–1721.
Kawaguchi, Y., Kovacs, J. J., McLaurin, A., Vance, J. M., Ito, A., and Yao, T. P. (2003). The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115, 727–738.
Keane, M. M., Ettenberg, S. A., Nau, M. M., Russell, E. K., and Lipkowitz, S. (1999). Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res 59, 734–741.
Kelly, W. K., O’Connor, O. A., Krug, L. M., Chiao, J. H., Heaney, M., Curley, T., MacGregore-Cortelli, B., Tong, W., Secrist, J. P., Schwartz, L., et al. (2005). Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J Clin Oncol 23, 3923–3931.
Khan, S. B., Maududi, T., Barton, K., Ayers, J., and Alkan, S. (2004). Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma. Br J Haematol 125, 156–161.
Kijima, M., Yoshida, M., Sugita, K., Horinouchi, S., and Beppu, T. (1993). Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem 268, 22429–22435.
Kim, D., Lee, I. S., Jung, J. H., Lee, C. O., and Choi, S. U. (1999a). Psammaplin A, a natural phenolic compound, has inhibitory effect on human topoisomerase II and is cytotoxic to cancer cells. Anticancer Res 19, 4085–4090.
Kim, D., Lee, I. S., Jung, J. H., and Yang, S. I. (1999b). Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistant Staphylococcus aureus and the DNA gyrase-inhibitory activity. Arch Pharm Res 22, 25–29.
Kim, D. H., Kim, M., and Kwon, H. J. (2003). Histone deacetylase in carcinogenesis and its inhibitors as anti-cancer agents. J Biochem Mol Biol 36, 110–119.
Kim, J. H., Shin, J. H., and Kim, I. H. (2004a). Susceptibility and radiosensitization of human glioblastoma cells to trichostatin A, a histone deacetylase inhibitor. Int J Radiat Oncol Biol Phys 59, 1174–1180.
Kim, J. S., Jeung, H. K., Cheong, J. W., Maeng, H., Lee, S. T., Hahn, J. S., Ko, Y. W,. and Min, Y. H. (2004b). Apicidin potentiates the imatinib-induced apoptosis of Bcr-Abl-positive human leukaemia cells by enhancing the activation of mitochondria-dependent caspase cascades. Br J Haematol 124, 166–178.
Kim, J. S., Lee, S., Lee, T., Lee, Y. W., and Trepel, J. B. (2001a). Transcriptional activation of p21(WAF1/CIP1) by apicidin, a novel histone deacetylase inhibitor. Biochem Biophys Res Commun 281, 866–871.
Kim, M. S., Kwon, H. J., Lee, Y. M., Baek, J. H., Jang, J. E., Lee, S. W., Moon, E. J., Kim, H. S., Lee, S. K., Chung, H. Y., et al. (2001b). Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat Med 7, 437–443.
Kim, S. H., Ahn, S., Han, J. W., Lee, H. W., Lee, H. Y., Lee, Y. W., Kim, M. R., Kim, K. W., Kim, W. B., and Hong, S. (2004c). Apicidin is a histone deacetylase inhibitor with anti-invasive and anti-angiogenic potentials. Biochem Biophys Res Commun 315, 964–970.
Kim, Y. B., Lee, K. H., Sugita, K., Yoshida, M., and Horinouchi, S. (1999c). Oxamflatin is a novel antitumor compound that inhibits mammalian histone deacetylase. Oncogene 18, 2461–2470.
Klisovic, D. D., Katz, S. E., Effron, D., Klisovic, M. I., Wickham, J., Parthun, M. R., Guimond, M., and Marcucci, G. (2003a). Depsipeptide (FR901228) inhibits proliferation and induces apoptosis in primary and metastatic human uveal melanoma cell lines. Invest Ophthalmol Vis Sci 44, 2390–2398.
Klisovic, D. D., Klisovic, M. I., Effron, D., Liu, S., Marcucci, G., and Katz, S. E. (2005). Depsipeptide inhibits migration of primary and metastatic uveal melanoma cell lines in vitro: a potential strategy for uveal melanoma. Melanoma Res 15, 147–153.
Klisovic, M. I., Maghraby, E. A., Parthun, M. R., Guimond, M., Sklenar, A. R., Whitman, S. P., Chan, K. K., Murphy, T., Anon, J., Archer, K. J., et al. (2003b). Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells. Leukemia 17, 350–358.
Kouraklis, G. and Theocharis, S. (2002). Histone deacetylase inhibitors and anticancer therapy. Curr Med Chem Anti-Canc Agents 2, 477–484.
Kouzarides, T. (1999). Histone acetylases and deacetylases in cell proliferation. Curr Opin Genet Dev 9, 40–48.
Kovacs, J. J., Murphy, P. J., Gaillard, S., Zhao, X., Wu, J. T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B., and Yao, T. P. (2005). HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18, 601–607.
Kurdistani, S. K. and Grunstein, M. (2003). Histone acetylation and deacetylation in yeast. Nat Rev Mol Cell Biol 4, 276–284.
Kwon, H. J., Owa, T., Hassig, C. A., Shimada, J., and Schreiber, S. L. (1998). Depudecin induces morphological reversion of transformed fibroblasts via the inhibition of histone deacetylase. Proc Natl Acad Sci USA 95, 3356–3361.
Kwon, H. J., Kim, M. S., Kim, M. J., Nakajima, H., and Kim, K. W. (2002a). Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. Int J Cancer 97, 290–296.
Kwon, S. H., Ahn, S. H., Kim, Y. K., Bae, G. U., Yoon, J. W., Hong, S., Lee, H. Y., Lee, Y. W., Lee, H. W., and Han, J. W. (2002b). Apicidin, a histone deacetylase inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells. J Biol Chem 277, 2073–2080.
Lagger, G., O’Carroll, D., Rembold, M., Khier, H., Tischler, J., Weitzer, G., Schuettengruber, B., Hauser, C., Brunmeir, R., Jenuwein, T., and Seiser, C. (2002). Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression. EMBO J 21, 2672–2681.
Lallemand, F., Courilleau, D., Sabbah, M., Redeuilh, G., and Mester, J. (1996). Direct inhibition of the expression of cyclin D1 gene by sodium butyrate. Biochem Biophys Res Commun 229, 163–169.
Langley, E., Pearson, M., Faretta, M., Bauer, U. M., Frye, R. A., Minucci, S., Pelicci, P. G., and Kouzarides, T. (2002). Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21, 2383–2396.
Lavelle, D., Chen, Y. H., Hankewych, M., and DeSimone, J. (2001). Histone deacetylase inhibitors increase p21(WAF1) and induce apoptosis of human myeloma cell lines independent of decreased IL-6 receptor expression. Am J Hematol 68, 170–178.
Lea, M. A., Randolph, V. M., and Patel, M. (1999). Increased acetylation of histones induced by diallyl disulfide and structurally related molecules. Int J Oncol 15, 347–352.
Lee, B. I., Park, S. H., Kim, J. W., Sausville, E. A., Kim, H. T., Nakanishi, O., Trepel, J. B., and Kim, S. J. (2001). MS-275, a histone deacetylase inhibitor, selectively induces transforming growth factor beta type II receptor expression in human breast cancer cells. Cancer Res 61, 931–934.
Lin, R. J., Nagy, L., Inoue, S., Shao, W., Miller, W. H., Jr., and Evans, R. M. (1998). Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature 391, 811–814.
Liotta, L. A., Steeg, P. S., and Stetler-Stevenson, W. G. (1991). Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64, 327–336.
Liu, F., Dowling, M., Yang, X. J., and Kao, G. D. (2004). Caspase-mediated specific cleavage of human histone deacetylase 4. J Biol Chem 279, 34537–34546.
Liu, L. T., Chang, H. C., Chiang, L. C., and Hung, W. C. (2003). Histone deacetylase inhibitor up-regulates RECK to inhibit MMP-2 activation and cancer cell invasion. Cancer Res 63, 3069–3072.
Luo, J., Su, F., Chen, D., Shiloh, A., and Gu, W. (2000). Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408, 377–381.
Luo, J., Nikolaev, A. Y., Imai, S., Chen, D., Su, F., Shiloh, A., Guarente, L., and Gu, W. (2001). Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107, 137–148.
Luo, X., Budihardjo, I., Zou, H., Slaughter, C., and Wang, X. (1998). Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 94, 481–490.
Maggio, S. C., Rosato, R. R., Kramer, L. B., Dai, Y., Rahmani, M., Paik, D. S., Czarnik, A. C., Payne, S. G., Spiegel, S., and Grant, S. (2004). The histone deacetylase inhibitor MS-275 interacts synergistically with fludarabine to induce apoptosis in human leukemia cells. Cancer Res 64, 2590–2600.
Mai, A., Massa, S., Rotili, D., Cerbara, I., Valente, S., Pezzi, R., Simeoni, S., and Ragno, R. (2005). Histone deacetylation in epigenetics: an attractive target for anticancer therapy. Med Res Rev 25, 261–309.
Marks, P., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., and Kelly, W. K. (2001a). Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 1, 194–202.
Marks, P. A. and Jiang, X. (2005). Histone deacetylase inhibitors in programmed cell death and cancer therapy. Cell Cycle 4, 549–551.
Marks, P. A. and Rifkind, R. A. (1988). Hexamethylene bisacetamide-induced differentiation of transformed cells: molecular and cellular effects and therapeutic application. Int J Cell Cloning 6, 230–240.
Marks, P. A., Richon, V. M., and Rifkind, R. A. (1996). Cell cycle regulatory proteins are targets for induced differentiation of transformed cells: molecular and clinical studies employing hybrid polar compounds. Int J Hematol 63, 1–17.
Marks, P. A., Richon, V. M., Breslow, R., and Rifkind, R. A. (2001b). Histone deacetylase inhibitors as new cancer drugs. Curr Opin Oncol 13, 477–483.
Marks, P. A., Miller, T., and Richon, V. M. (2003). Histone deacetylases. Curr Opin Pharmacol 3, 344–351.
Marks, P. A., Richon, V. M., Miller, T., and Kelly, W. K. (2004). Histone deacetylase inhibitors. Adv Cancer Res 91, 137–168.
McIntyre, A., Gibson, P. R., and Young, G. P. (1993). Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 34, 386–391.
McKinsey, T. A. and Olson, E. N. (2005). Toward transcriptional therapies for the failing heart: chemical screens to modulate genes. J Clin Invest 115, 538–546.
McLaughlin, F. and La Thangue, N. B. (2004). Histone deacetylase inhibitors open new doors in cancer therapy. Biochem Pharmacol 68, 1139–1144.
Meinke, P. T. and Liberator, P. (2001). Histone deacetylase: a target for antiproliferative and antiprotozoal agents. Curr Med Chem 8, 211–235.
Meinke, P. T., Colletti, S. L., Doss, G., Myers, R. W., Gurnett, A. M., Dulski, P. M., Darkin-Rattray, S. J., Allocco, J. J., Galuska, S., Schmatz, D. M., et al. (2000). Synthesis of apicidin-derived quinolone derivatives: parasite-selective histone deacetylase inhibitors and antiproliferative agents. J Med Chem 43, 4919–4922.
Michaelis, M., Michaelis, U. R., Fleming, I., Suhan, T., Cinatl, J., Blaheta, R. A., Hoffmann, K., Kotchetkov, R., Busse, R., Nau, H., and Cinatl, J., Jr. (2004). Valproic acid inhibits angiogenesis in vitro and in vivo. Mol Pharmacol 65, 520–527.
Michaelis, M., Suhan, T., Michaelis, U. R., Beek, K., Rothweiler, F., Tausch, L., Werz, O., Eikel, D., Zornig, M., Nau, H., et al. (2005). Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells. Cell Death Differ 13(3), 446–453.
Mie Lee, Y., Kim, S. H., Kim, H. S., Jin Son, M., Nakajima, H., Jeong Kwon, H., and Kim, K. W. (2003). Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1alpha activity. Biochem Biophys Res Commun 300, 241–246.
Mitsiades, C. S., Poulaki, V., McMullan, C., Negri, J., Fanourakis, G., Goudopoulou, A., Richon, V. M., Marks, P. A., and Mitsiades, N. (2005). Novel histone deacetylase inhibitors in the treatment of thyroid cancer. Clin Cancer Res 11, 3958–3965.
Mitsiades, N., Mitsiades, C. S., Richardson, P. G., McMullan, C., Poulaki, V., Fanourakis, G., Schlossman, R., Chauhan, D., Munshi, N. C., Hideshima, T., et al. (2003). Molecular sequelae of histone deacetylase inhibition in human malignant B cells. Blood 101, 4055–4062.
Momparler, R. L. (2003). Cancer epigenetics. Oncogene 22, 6479–6483.
Monneret, C. (2005). Histone deacetylase inhibitors. Eur J Med Chem 40, 1–13.
Mori, N., Matsuda, T., Tadano, M., Kinjo, T., Yamada, Y., Tsukasaki, K., Ikeda, S., Yamasaki, Y., Tanaka, Y., Ohta, T., et al. (2004). Apoptosis induced by the histone deacetylase inhibitor FR901228 in human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells. J Virol 78, 4582–4590.
Murakami, J., Asaumi, J., Maki, Y., Tsujigiwa, H., Kuroda, M., Nagai, N., Yanagi, Y., Inoue, T., Kawasaki, S., Tanaka, N., et al. (2004). Effects of demethylating agent 5-aza-2(f)-deoxycytidine and histone deacetylase inhibitor FR901228 on maspin gene expression in oral cancer cell lines. Oral Oncol 40, 597–603.
Myzak, M. C., Karplus, P. A., Chung, F. L., and Dashwood, R. H. (2004). A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res 64, 5767–5774.
Myzak, M. C., Hardin, K., Wang, R., Dashwood, R. H., and Ho, E. (2005). Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP, and PC-3 prostate epithelial cells. Carcinogenesis 27, 811–819.
Nagane, M., Pan, G., Weddle, J. J., Dixit, V. M., Cavenee, W. K., and Huang, H. J. (2000). Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis-inducing ligand in vitro and in vivo. Cancer Res 60, 847–853.
Nam, N. H. and Parang, K. (2003). Current targets for anticancer drug discovery. Curr Drug Targets 4, 159–179.
Nebbioso, A., Clarke, N., Voltz, E., Germain, E., Ambrosino, C., Bontempo, P., Alvarez, R., Schiavone, E. M., Ferrara, F., Bresciani, F., et al. (2005). Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells. Nat Med 11, 77–84.
Neuzil, J., Swettenham, E., and Gellert, N. (2004). Sensitization of mesothelioma to TRAIL apoptosis by inhibition of histone deacetylase: role of Bcl-xL down-regulation. Biochem Biophys Res Commun 314, 186–191.
Nicolaou, K. C., Hughes, R., Pfefferkorn, J. A., and Barluenga, S. (2001). Optimization and mechanistic studies of psammaplin A type antibacterial agents active against methicillin-resistant Staphylococcus aureus (MRSA). Chemistry 7, 4296–4310.
Nimmanapalli, R., Fuino, L., Stobaugh, C., Richon, V., and Bhalla, K. (2003). Cotreatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) enhances imatinib-induced apoptosis of Bcr-Abl-positive human acute leukemia cells. Blood 101, 3236–3239.
Nome, R. V., Bratland, A., Harman, G., Fodstad, O., Andersson, Y., and Ree, A. H. (2005). Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death. Mol Cancer Ther 4, 1231–1238.
O’Brien, T., Cranston, D., Fuggle, S., Bicknell, R., and Harris, A. L. (1995). Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res 55, 510–513.
O’Shea, J. J., Kanno, Y., Chen, X., and Levy, D. E. (2005). Cell signaling. Stat acetylation–a key facet of cytokine signaling? Science 307, 217–218.
Oikawa, T., Onozawa, C., Inose, M., and Sasaki, M. (1995). Depudecin, a microbial metabolite containing two epoxide groups, exhibits anti-angiogenic activity in vivo. Biol Pharm Bull 18, 1305–1307.
Papeleu, P., Vanhaecke, T., Elaut, G., Vinken, M., Henkens, T., Snykers, S., and Rogiers, V. (2005). Differential effects of histone deacetylase inhibitors in tumor and normal cells-what is the toxicological relevance? Crit Rev Toxicol 35, 363–378.
Park, J. H., Jung, Y., Kim, T. Y., Kim, S. G., Jong, H. S., Lee, J. W., Kim, D. K., Lee, J. S., Kim, N. K., Kim, T. Y., and Bang, Y. J. (2004). Class I histone deacetylase-selective novel synthetic inhibitors potently inhibit human tumor proliferation. Clin Cancer Res 10, 5271–5281.
Park, S. H., Lee, S. R., Kim, B. C., Cho, E. A., Patel, S. P., Kang, H. B., Sausville, E. A., Nakanishi, O., Trepel, J. B., Lee, B. I., and Kim, S. J. (2002). Transcriptional regulation of the transforming growth factor beta type II receptor gene by histone acetyltransferase and deacetylase is mediated by NF-Y in human breast cancer cells. J Biol Chem 277, 5168–5174.
Park, Y., Liu, Y., Hong, J., Lee, C. O., Cho, H., Kim, D. K., Im, K. S., and Jung, J. H. (2003). New bromotyrosine derivatives from an association of two sponges, Jaspis wondoensis and Poecillastra wondoensis. J Nat Prod 66, 1495–1498.
Parker, S. B., Eichele, G., Zhang, P., Rawls, A., Sands, A. T., Bradley, A., Olson, E. N., Harper, J. W., and Elledge, S. J. (1995). p53-independent expression of p21Cip1 in muscle and other terminally differentiating cells. Science 267, 1024–1027.
Paroni, G., Mizzau, M., Henderson, C., Del Sal, G., Schneider, C. and Brancolini, C. (2004). Caspase-dependent regulation of histone deacetylase 4 nuclear-cytoplasmic shuttling promotes apoptosis. Mol Biol Cell 15, 2804–2818.
Pham, N. B., Butler, M. S., and Quinn, R. J. (2000). Isolation of psammaplin A 11d-sulfate and bisaprasin 11–sulfate from the marine sponge Aplysinella rhax. J Nat Prod 63, 393–395.
Pili, R., Kruszewski, M. P., Hager, B. W., Lantz, J., and Carducci, M. A. (2001). Combination of phenylbutyrate and 13-cis retinoic acid inhibits prostate tumor growth and angiogenesis. Cancer Res 61, 1477–1485.
Pina, I. C., Gautschi, J. T., Wang, G. Y., Sanders, M. L., Schmitz, F. J., France, D., Cornell-Kennon, S., Sambucetti, L. C., Remiszewski, S. W., Perez, L. B., et al. (2003). Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. J Org Chem 68, 3866–3873.
Plass, C. (2002). Cancer epigenomics. Hum Mol Genet 11, 2479–2488.
Qian, D. Z., Wang, X., Kachhap, S. K., Kato, Y., Wei, Y., Zhang, L., Atadja, P., and Pili, R. (2004). The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res 64, 6626–6634.
Qian, D. Z., Kato, Y., Shabbeer, S., Wei, Y., Verheul, H. M., Salumbides, B., Sanni, T., Atadja, P., and Pili, R. (2006). Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res 12, 634–642.
Qiu, L., Burgess, A., Fairlie, D. P., Leonard, H., Parsons, P. G., and Gabrielli, B. G. (2000). Histone deacetylase inhibitors trigger a G2 checkpoint in normal cells that is defective in tumor cells. Mol Biol Cell 11, 2069–2083.
Quivy, V. and Van Lint, C. (2004). Regulation at multiple levels of NF-kappaB-mediated transactivation by protein acetylation. Biochem Pharmacol 68, 1221–1229.
Rahmani, M., Reese, E., Dai, Y., Bauer, C., Payne, S. G., Dent, P., Spiegel, S., and Grant, S. (2005). Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species. Cancer Res 65, 2422–2432.
Ravery, V., Jouanneau, J., Gil Diez, S., Abbou, C. C., Caruelle, J. P., Barritault, D., and Chopin, D. K. (1992). Immunohistochemical detection of acidic fibroblast growth factor in bladder transitional cell carcinoma. Urol Res 20, 211–214.
Ravi, R., Bedi, G. C., Engstrom, L. W., Zeng, Q., Mookerjee, B., Gelinas, C., Fuchs, E. J., and Bedi, A. (2001). Regulation of death receptor expression and TRAIL/Apo2L-induced apoptosis by NF-kappaB. Nat Cell Biol 3, 409–416.
Richon, V. M., Emiliani, S., Verdin, E., Webb, Y., Breslow, R., Rifkind, R. A., and Marks, P. A. (1998). A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases. Proc Natl Acad Sci USA 95, 3003–3007.
Riggs, M. G., Whittaker, R. G., Neumann, J. R., and Ingram, V. M. (1977). n-Butyrate causes histone modification in HeLa and Friend erythroleukaemia cells. Nature 268, 462–464.
Rocchi, P., Tonelli, R., Camerin, C., Purgato, S., Fronza, R., Bianucci, F., Guerra, F., Pession, A., and Ferreri, A. M. (2005). p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors (valproic acid, tributyrin and sodium butyrate) in neuroblastoma cells. Oncol Rep 13, 1139–1144.
Rosato, R. R., Wang, Z., Gopalkrishnan, R. V., Fisher, P. B., and Grant, S. (2001). Evidence of a functional role for the cyclin-dependent kinase-inhibitor p21WAF1/CIP1/MDA6 in promoting differentiation and preventing mitochondrial dysfunction and apoptosis induced by sodium butyrate in human myelomonocytic leukemia cells (U937). Int J Oncol 19, 181–191.
Rosato, R. R., Almenara, J. A., Dai, Y., and Grant, S. (2003a). Simultaneous activation of the intrinsic and extrinsic pathways by histone deacetylase (HDAC) inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically induces mitochondrial damage and apoptosis in human leukemia cells. Mol Cancer Ther 2, 1273–1284.
Rosato, R. R., Almenara, J. A., and Grant, S. (2003b). The histone deacetylase inhibitor MS-275 promotes differentiation or apoptosis in human leukemia cells through a process regulated by generation of reactive oxygen species and induction of p21CIP1/WAF1 1. Cancer Res 63, 3637–3645.
Rossig, L., Li, H., Fisslthaler, B., Urbich, C., Fleming, I., Forstermann, U., Zeiher, A. M., and Dimmeler, S. (2002). Inhibitors of histone deacetylation downregulate the expression of endothelial nitric oxide synthase and compromise endothelial cell function in vasorelaxation and angiogenesis. Circ Res 91, 837–844.
Ryan, Q. C., Headlee, D., Acharya, M., Sparreboom, A., Trepel, J. B., Ye, J., Figg, W. D., Hwang, K., Chung, E. J., Murgo, A., et al. (2005). Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma. J Clin Oncol 23, 3912–3922.
Sakajiri, S., Kumagai, T., Kawamata, N., Saitoh, T., Said, J. W., and Koeffler, H. P. (2005). Histone deacetylase inhibitors profoundly decrease proliferation of human lymphoid cancer cell lines. Exp Hematol 33, 53–61.
Sandor, V., Bakke, S., Robey, R. W., Kang, M. H., Blagosklonny, M. V., Bender, J., Brooks, R., Piekarz, R. L., Tucker, E., Figg, W. D., et al. (2002). Phase I trial of the histone deacetylase inhibitor, depsipeptide (FR901228, NSC 630176), in patients with refractory neoplasms. Clin Cancer Res 8, 718–728.
Sartorius, U., Schmitz, I., and Krammer, P. H. (2001). Molecular mechanisms of death-receptor-mediated apoptosis. Chembiochem 2, 20–29.
Sasakawa, Y., Naoe, Y., Inoue, T., Sasakawa, T., Matsuo, M., Manda, T., and Mutoh, S. (2002). Effects of FK228, a novel histone deacetylase inhibitor, on human lymphoma U-937 cells in vitro and in vivo. Biochem Pharmacol 64, 1079–1090.
Sasakawa, Y., Naoe, Y., Noto, T., Inoue, T., Sasakawa, T., Matsuo, M., Manda, T., and Mutoh, S. (2003). Antitumor efficacy of FK228, a novel histone deacetylase inhibitor, depends on the effect on expression of angiogenesis factors. Biochem Pharmacol 66, 897–906.
Sato, N., Ohta, T., Kitagawa, H., Kayahara, M., Ninomiya, I., Fushida, S., Fujimura, T., Nishimura, G., Shimizu, K., and Miwa, K. (2004). FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells. Int J Oncol 24, 679–685.
Savickiene, J., Treigyte, G., Pivoriunas, A., Navakauskiene, R., and Magnusson, K. E. (2004). Sp1 and NF-kappaB transcription factor activity in the regulation of the p21 and FasL promoters during promyelocytic leukemia cell monocytic differentiation and its associated apoptosis. Ann NY Acad Sci 1030, 569–577.
Sawa, H., Murakami, H., Ohshima, Y., Murakami, M., Yamazaki, I., Tamura, Y., Mima, T., Satone, A., Ide, W., Hashimoto, I., and Kamada, H. (2002). Histone deacetylase inhibitors such as sodium butyrate and trichostatin A inhibit vascular endothelial growth factor (VEGF) secretion from human glioblastoma cells. Brain Tumor Pathol 19, 77–81.
Sawa, H., Murakami, H., Kumagai, M., Nakasato, M., Yamauchi, S., Matsuyama, N., Tamura, Y., Satone, A., Ide, W., Hashimoto, I., and Kamada, H. (2004). Histone deacetylase inhibitor, FK228, induces apoptosis and suppresses cell proliferation of human glioblastoma cells in vitro and in vivo. Acta Neuropathol (Berl) 107, 523–531.
Shankar, S., Singh, T. R., Chen, X., Thakkar, H., Firnin, J., and Srivastava, R. K. (2004a). The sequential treatment with ionizing radiation followed by TRAIL/Apo-2L reduces tumor growth and induces apoptosis of breast tumor xenografts in nude mice. Int J Oncol 24, 1133–1140.
Shankar, S., Singh, T. R., and Srivastava, R. K. (2004b). Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: intracellular mechanisms. Prostate 61, 35–49.
Shankar, S., Chen, X., and Srivastava, R. K. (2005a). Effects of sequential treatments with chemotherapeutic drugs followed by TRAIL on prostate cancer in vitro and in vivo. Prostate 62, 165–186.
Shankar, S., Singh, T. R., Fandy, T. E., Luetrakul, T., Ross, D. D., and Srivastava, R. K. (2005b). Interactive effects of histone deacetylase inhibitors and TRAIL on apoptosis in human leukemia cells: Involvement of both death receptor and mitochondrial pathways. Int J Mol Med 16, 1125–1138.
Shao, Y., Gao, Z., Marks, P. A., and Jiang, X. (2004). Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA 101, 18030–18035.
Shen, S., Li, J., and Casaccia-Bonnefil, P. (2005). Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J Cell Biol 169, 577–589.
Shetty, S., Graham, B. A., Brown, J. G., Hu, X., Vegh-Yarema, N., Harding, G., Paul, J. T., and Gibson, S. B. (2005). Transcription factor NF-kappaB differentially regulates death receptor 5 expression involving histone deacetylase 1. Mol Cell Biol 25, 5404–5416.
Shim, J. S., Lee, H. S., Shin, J., and Kwon, H. J. (2004). Psammaplin A, a marine natural product, inhibits aminopeptidase N and suppresses angiogenesis in vitro. Cancer Lett 203, 163–169.
Simonsson, M., Heldin, C. H., Ericsson, J., and Gronroos, E. (2005). The balance between acetylation and deacetylation controls Smad7 stability. J Biol Chem 280, 21797–21803.
Singh, T. R., Shankar, S., Chen, X., Asim, M., and Srivastava, R. K. (2003). Synergistic interactions of chemotherapeutic drugs and tumor necrosis factor-related apoptosis-inducing ligand/Apo-2 ligand on apoptosis and on regression of breast carcinoma in vivo. Cancer Res 63, 5390–5400.
Singh, T. R., Shankar, S., and Srivastava, R. K. (2005). HDAC inhibitors enhance the apoptosis-inducing potential of TRAIL in breast carcinoma. Oncogene 24, 4609–4623.
Souleimani, A. and Asselin, C. (1993). Regulation of c-myc expression by sodium butyrate in the colon carcinoma cell line Caco-2. FEBS Lett 326, 45–50.
Sowa, Y. and Sakai, T. (2000). Butyrate as a model for “gene-regulating chemoprevention and chemotherapy”. Biofactors 12, 283–287.
Sowa, Y., Orita, T., Minamikawa-Hiranabe, S., Mizuno, T., Nomura, H., and Sakai, T. (1999). Sp3, but not Sp1, mediates the transcriptional activation of the p21/WAF1/Cip1 gene promoter by histone deacetylase inhibitor. Cancer Res 59, 4266–4270.
Strahl, B. D. and Allis, C. D. (2000). The language of covalent histone modifications. Nature 403, 41–45.
Strait, K. A., Warnick, C. T., Ford, C. D., Dabbas, B., Hammond, E. H., and Ilstrup, S. J. (2005). Histone deacetylase inhibitors induce G2-checkpoint arrest and apoptosis in cisplatinum-resistant ovarian cancer cells associated with overexpression of the Bcl-2-related protein Bad. Mol Cancer Ther 4, 603–611.
Su, G. H., Sohn, T. A., Ryu, B., and Kern, S. E. (2000). A novel histone deacetylase inhibitor identified by high-throughput transcriptional screening of a compound library. Cancer Res 60, 3137–3142.
Subramanian, C., Opipari, A. W., Jr., Bian, X., Castle, V. P., and Kwok, R. P. (2005). Ku70 acetylation mediates neuroblastoma cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA 102, 4842–4847.
Suliman, A., Lam, A., Datta, R., and Srivastava, R. K. (2001). Intracellular mechanisms of TRAIL: apoptosis through mitochondrial-dependent and -independent pathways. Oncogene 20, 2122–2133.
Suzuki, T., Ando, T., Tsuchiya, K., Fukazawa, N., Saito, A., Mariko, Y., Yamashita, T., and Nakanishi, O. (1999). Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives. J Med Chem 42, 3001–3003.
Taghiyev, A. F., Guseva, N. V., Sturm, M. T., Rokhlin, O. W., and Cohen, M. B. (2005). Trichostatin A (TSA) Sensitizes the Human Prostatic Cancer Cell Line DU145 to Death Receptor Ligands Treatment. Cancer Biol Ther 4, 382–390.
Takai, N., Desmond, J. C., Kumagai, T., Gui, D., Said, J. W., Whittaker, S., Miyakawa, I., and Koeffler, H. P. (2004a). Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells. Clin Cancer Res 10, 1141–1149.
Takai, N., Kawamata, N., Gui, D., Said, J. W., Miyakawa, I., and Koeffler, H. P. (2004b). Human ovarian carcinoma cells: histone deacetylase inhibitors exhibit antiproliferative activity and potently induce apoptosis. Cancer 101, 2760–2770.
Takimoto, R., Kato, J., Terui, T., Takada, K., Kuroiwa, G., Wu, J., Ohnuma, H., Takahari, D., Kobune, M., Sato, Y., et al. (2005). Augmentation of Antitumor Effects of p53 Gene Therapy by Combination with HDAC Inhibitor. Cancer Biol Ther 4, 421–428.
Tang, X. X., Robinson, M. E., Riceberg, J. S., Kim, D. Y., Kung, B., Titus, T. B., Hayashi, S., Flake, A. W., Carpentieri, D., and Ikegaki, N. (2004). Favorable neuroblastoma genes and molecular therapeutics of neuroblastoma. Clin Cancer Res 10, 5837–5844.
Taunton, J., Hassig, C. A., and Schreiber, S. L. (1996). A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 272, 408–411.
Terui, T., Murakami, K., Takimoto, R., Takahashi, M., Takada, K., Murakami, T., Minami, S., Matsunaga, T., Takayama, T., Kato, J., and Niitsu, Y. (2003). Induction of PIG3 and NOXA through acetylation of p53 at 320 and 373 lysine residues as a mechanism for apoptotic cell death by histone deacetylase inhibitors. Cancer Res 63, 8948–8954.
Thevenet, L., Mejean, C., Moniot, B., Bonneaud, N., Galeotti, N., Aldrian-Herrada, G., Poulat, F., Berta, P., Benkirane, M., and Boizet-Bonhoure, B. (2004). Regulation of human SRY subcellular distribution by its acetylation/deacetylation. EMBO J 23, 3336–3345.
Tissenbaum, H. A. and Guarente, L. (2001). Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227–230.
Toth, K. F., Knoch, T. A., Wachsmuth, M., Frank-Stohr, M., Stohr, M., Bacher, C. P., Muller, G., and Rippe, K. (2004). Trichostatin A-induced histone acetylation causes decondensation of interphase chromatin. J Cell Sci 117, 4277–4287.
Touma, S. E., Goldberg, J. S., Moench, P., Guo, X., Tickoo, S. K., Gudas, L. J., and Nanus, D. M. (2005). Retinoic acid and the histone deacetylase inhibitor trichostatin a inhibit the proliferation of human renal cell carcinoma in a xenograft tumor model. Clin. Cancer Res 11, 3558–3566.
Trock, B., Lanza, E., and Greenwald, P. (1990). Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence. J Natl Cancer Inst 82, 650–661.
Tsatsoulis, A. (2002). The role of apoptosis in thyroid disease. Minerva Med 93, 169–180.
Tsuji, N., Kobayashi, M., Nagashima, K., Wakisaka, Y., and Koizumi, K. (1976). A new antifungal antibiotic, trichostatin. J Antibiot (Tokyo) 29, 1–6.
Van Lint, C., Emiliani, S., and Verdin, E. (1996). The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr 5, 245–253.
Vanhaecke, T., Henkens, T., Kass, G. E., and Rogiers, V. (2004a). Effect of the histone deacetylase inhibitor trichostatin A on spontaneous apoptosis in various types of adult rat hepatocyte cultures. Biochem Pharmacol 68, 753–760.
Vanhaecke, T., Papeleu, P., Elaut, G., and Rogiers, V. (2004b). Trichostatin A-like hydroxamate histone deacetylase inhibitors as therapeutic agents: toxicological point of view. Curr Med Chem 11, 1629–1643.
Vanoosten, R. L., Moore, J. M., Karacay, B., and Griffith, T. S. (2005). Histone Deacetylase Inhibitors Modulate Renal Cell Carcinoma Sensitivity to TRAIL/Apo-2L-induced Apoptosis by Enhancing TRAIL-R2 Expression. Cancer Biol Ther 4, 1104–1112.
Varshochi, R., Halim, F., Sunters, A., Alao, J. P., Madureira, P. A., Hart, S. M., Ali, S., Vigushin, D. M., Coombes, R. C., and Lam, E. W. (2005). ICI182, 780 induces p21Waf1 gene transcription through releasing histone deacetylase 1 and estrogen receptor alpha from Sp1 sites to induce cell cycle arrest in MCF-7 breast cancer cell line. J Biol Chem 280, 3185–3196.
Vaziri, H., Dessain, S. K., Ng Eaton, E., Imai, S. I., Frye, R. A., Pandita, T. K., Guarente, L., and Weinberg, R. A. (2001). hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107, 149–159.
Verdin, E., Dequiedt, F., and Kasler, H. G. (2003). Class II histone deacetylases: versatile regulators. Trends Genet 19, 286–293.
Verhagen, A. M., Ekert, P. G., Pakusch, M., Silke, J., Connolly, L. M., Reid, G. E., Moritz, R. L., Simpson, R. J., and Vaux, D. L. (2000). Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102, 43–53.
Vigushin, D. M. and Coombes, R. C. (2002). Histone deacetylase inhibitors in cancer treatment. Anticancer Drugs 13, 1–13.
Wang, S., Yan-Neale, Y., Fischer, D., Zeremski, M., Cai, R., Zhu, J., Asselbergs, F., Hampton, G., and Cohen, D. (2003). Histone deacetylase 1 represses the small GTPase RhoB expression in human nonsmall lung carcinoma cell line. Oncogene 22, 6204–6213.
Wang, X. F., Qian, D. Z., Ren, M., Kato, Y., Wei, Y., Zhang, L., Fansler, Z., Clark, D., Nakanishi, O., and Pili, R. (2005). Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase inhibitor MS-275 in human renal cell carcinoma. Clin Cancer Res 11, 3535–3542.
Wang, Z. M., Hu, J., Zhou, D., Xu, Z. Y., Panasci, L. C., and Chen, Z. P. (2002). Trichostatin A inhibits proliferation and induces expression of p21WAF and p27 in human brain tumor cell lines. Ai Zheng 21, 1100–1105.
Warrell, R. P., Jr., He, L. Z., Richon, V., Calleja, E., and Pandolfi, P. P. (1998). Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Natl Cancer Inst 90, 1621–1625.
Wei, M. C., Lindsten, T., Mootha, V. K., Weiler, S., Gross, A., Ashiya, M., Thompson, C. B., and Korsmeyer, S. J. (2000). tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14, 2060–2071.
Wiedmann, M. W. and Caca, K. (2005). Molecularly targeted therapy for gastrointestinal cancer. Curr Cancer Drug Targets 5, 171–193.
Williams, R. J. (2001). Trichostatin A, an inhibitor of histone deacetylase, inhibits hypoxia-induced angiogenesis. Expert Opin Investig Drugs 10, 1571–1573.
Xiao, H., Hasegawa, T., Miyaishi, O., Ohkusu, K., and Isobe, K. (1997). Sodium butyrate induces NIH3T3 cells to senescence-like state and enhances promoter activity of p21WAF/CIP1 in p53-independent manner. Biochem Biophys Res Commun 237, 457–460.
Xiong, Y., Dowdy, S. C., Podratz, K. C., Jin, F., Attewell, J. R., Eberhardt, N. L., and Jiang, S. W. (2005). Histone deacetylase inhibitors decrease DNA methyltransferase-3B messenger RNA stability and down-regulate de novo DNA methyltransferase activity in human endometrial cells. Cancer Res 65, 2684–2689.
Xu, W. S., Perez, G., Ngo, L., Gui, C. Y., and Marks, P. A. (2005a). Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects. Cancer Res 65, 7832–7839.
Xu, Y., Voelter-Mahlknecht, S., and Mahlknecht, U. (2005b). The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl, c-Myc and HDAC3 in chronic myeloid leukemia cell lines. Int J Mol Med 15, 169–172.
Yamashita, Y., Shimada, M., Harimoto, N., Rikimaru, T., Shirabe, K., Tanaka, S., and Sugimachi, K. (2003). Histone deacetylase inhibitor trichostatin A induces cell-cycle arrest/apoptosis and hepatocyte differentiation in human hepatoma cells. Int J Cancer 103, 572–576.
Yang, W. M., Inouye, C., Zeng, Y., Bearss, D., and Seto, E. (1996). Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Proc Natl Acad Sci USA 93, 12845–12850.
Yang, X. J. and Gregoire, S. (2005). Class II histone deacetylases: from sequence to function, regulation, and clinical implication. Mol Cell Biol 25, 2873–2884.
Yang, Y., Hou, H., Haller, E. M., Nicosia, S. V., and Bai, W. (2005). Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J 24, 1021–1032.
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., and Mayo, M. W. (2004). Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23, 2369–2380.
Yokota, T., Matsuzaki, Y., Miyazawa, K., Zindy, F., Roussel, M. F., and Sakai, T. (2004). Histone deacetylase inhibitors activate INK4d gene through Sp1 site in its promoter. Oncogene 23, 5340–5349.
Yoshida, M., Hoshikawa, Y., Koseki, K., Mori, K., and Beppu, T. (1990a). Structural specificity for biological activity of trichostatin A, a specific inhibitor of mammalian cell cycle with potent differentiation-inducing activity in Friend leukemia cells. J Antibiot (Tokyo) 43, 1101–1106.
Yoshida, M., Kijima, M., Akita, M., and Beppu, T. (1990b). Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 265, 17174–17179.
Yoshida, M., Shimazu, T., and Matsuyama, A. (2003). Protein deacetylases: enzymes with functional diversity as novel therapeutic targets. Prog Cell Cycle Res 5, 269–278.
Yu, C., Rahmani, M., Conrad, D., Subler, M., Dent, P., and Grant, S. (2003). The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571. Blood 102, 3765–3774.
Yuan, Z. L., Guan, Y. J., Chatterjee, D., and Chin, Y. E. (2005). Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 307, 269–273.
Zgouras, D., Becker, U., Loitsch, S. and Stein, J. (2004). Modulation of angiogenesis-related protein synthesis by valproic acid. Biochem Biophys Res Commun 316, 693–697.
Zhang, X., Wei, L., Yang, Y. and Yu, Q. (2004a). Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway. J. Cell Biochem. 93, 819–829.
Zhang, X. D., Gillespie, S. K., Borrow, J. M., and Hersey, P. (2003). The histone deacetylase inhibitor suberic bishydroxamate: a potential sensitizer of melanoma to TNF-related apoptosis-inducing ligand (TRAIL) induced apoptosis. Biochem Pharmacol 66, 1537–1545.
Zhang, X. D., Gillespie, S. K., Borrow, J. M., and Hersey, P. (2004b). The histone deacetylase inhibitor suberic bishydroxamate regulates the expression of multiple apoptotic mediators and induces mitochondria-dependent apoptosis of melanoma cells. Mol Cancer Ther 3, 425–435.
Zhang, Y., Adachi, M., Zhao, X., Kawamura, R., and Imai, K. (2004c). Histone deacetylase inhibitors FK228, N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl) amino- methyl]benzamide and m-carboxycinnamic acid bis-hydroxamide augment radiation-induced cell death in gastrointestinal adenocarcinoma cells. Int J Cancer 110, 301–308.
Zhang, Y., Jung, M., Dritschilo, A., and Jung, M. (2004d). Enhancement of radiation sensitivity of human squamous carcinoma cells by histone deacetylase inhibitors. Radiat Res 161, 667–674.
Zhu, W. G., Lakshmanan, R. R., Beal, M. D., and Otterson, G. A. (2001). DNA methyltransferase inhibition enhances apoptosis induced by histone deacetylase inhibitors. Cancer Res 61, 1327–1333.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science + Business Media B.V
About this chapter
Cite this chapter
Shankar, S., Srivastava, R.K. (2008). Histone Deacetylase Inhibitors: Mechanisms and Clinical Significance in Cancer: HDAC Inhibitor-Induced Apoptosis. In: Programmed Cell Death in Cancer Progression and Therapy. Advances in Experimental Medicine and Biology, vol 615. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6554-5_13
Download citation
DOI: https://doi.org/10.1007/978-1-4020-6554-5_13
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-6553-8
Online ISBN: 978-1-4020-6554-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)