Applied Microbiology and Biotechnology

, Volume 67, Issue 4, pp 453–468

Medicinal mushroom modulators of molecular targets as cancer therapeutics

  • Ben-Zion Zaidman
  • Majed Yassin
  • Jamal Mahajna
  • Solomon P. Wasser
Mini-Review

Abstract

Empirical approaches to discover anticancer drugs and cancer treatments have made limited progress in the past several decades in finding a cure for cancer. The expanded knowledge of the molecular basis of tumorigenesis and metastasis, together with the inherently vast structural diversity of natural compounds found in mushrooms, provided unique opportunities for discovering new drugs that rationally target the abnormal molecular and biochemical signals leading to cancer. This review focuses on mushroom low-molecular-weight secondary metabolites targeting processes such as apoptosis, angiogenesis, metastasis, cell cycle regulation, and signal transduction cascades. Also discussed in this review are high-molecular-weight polysaccharides or polysaccharide–protein complexes from mushrooms that appear to enhance innate and cell-mediated immune responses, exhibit antitumor activities in animals and humans, and demonstrate the anticancer properties of selenium compounds accumulated in mushrooms.

References

  1. Adachi Y, Ishii T, Ikeda Y, Hoshino A, Tamura H, Aketagawa J, Tanaka S, Ohno N (2004) Characterization of beta-glucan recognition site on C-type lectin, Dectin 1. Infect Immun 72:4159–4171CrossRefPubMedGoogle Scholar
  2. Adachi Y, Okazaki M, Ohno N, Yadomae T (1994) Enhancement of cytokine production by macrophages stimulated with (1→3)-beta-d-glucan, grifolan (GRN), isolated from Grifola frondosa. Biol Pharm Bull 17:1554–1560PubMedGoogle Scholar
  3. Ahmed S, Owen CP, James K, Sampson L, Patel CK (2002) Review of estrone sulfatase and its inhibitors-an important new target against hormone dependent breast cancer. Curr Med Chem 9:263–273PubMedGoogle Scholar
  4. Akihisa T, Mizushina Y, Ukiya M, Oshikubo M, Kondo S, Kimura Y, Suzuki T, Tai T (2004) Dehydrotrametenonic acid and dehydroeburiconic acid from Poria cocos and their inhibitory effects on eukaryotic DNA polymerase alpha and beta. Biosci Biotechnol Biochem 68:448–450CrossRefPubMedGoogle Scholar
  5. Anonymous (2003) Development of Flammulina velutipes with anticancer function. RDA E-Newsl 2Google Scholar
  6. Ariga A, Namekawa J, Matsumoto N, Inoue J, Umezawa K (2002) Inhibition of tumor necrosis factor-alpha-induced nuclear translocation and activation of NF-kappa B by dehydroxymethylepoxyquinomicin. J Biol Chem 277:24625–24630CrossRefPubMedGoogle Scholar
  7. Awadh Ali NA, Mothana RA, Lesnau A, Pilgrim H, Lindequist U (2003) Antiviral activity of Inonotus hispidus. Fitoterapia 74:483–485CrossRefPubMedGoogle Scholar
  8. Battle J, Ha T, Li C, Della Beffa V, Rice P, Kalbfleisch J, Browder W, Williams D (1998) Ligand binding to the (1→3)-beta-d-glucan receptor stimulates NF-kappa B activation, but not apoptosis in U937 cells. Biochem Biophys Res Commun 249:499–504CrossRefPubMedGoogle Scholar
  9. Beecken WD, Kramer W, Jonas D (2000) New molecular mediators in tumor angiogenesis. J Cell Mol Med 4:262–269PubMedGoogle Scholar
  10. Berg WJ, Schwartz L, Yu R, Mazumdar M, Motzer RJ (2001) Phase II trial of irofulven (6-hydroxymethylacylfulvene) for patients with advanced renal cell carcinoma. Invest New Drugs 19:317–320CrossRefPubMedGoogle Scholar
  11. Berns H, Humar R, Hengerer B, Kiefer FN, Battegay EJ (2000) RACK1 is up-regulated in angiogenesis and human carcinomas. FASEB J 14:2549–2558CrossRefPubMedGoogle Scholar
  12. Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME (1999) Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med 221:281–293CrossRefPubMedGoogle Scholar
  13. Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S (2003) Dectin-1 mediates the biological effects of beta-glucans. J Exp Med 197:1119–1124CrossRefPubMedGoogle Scholar
  14. Burk RF (2002) Selenium, an antioxidant nutrient. Nutr Clin Care 5:75–79CrossRefPubMedGoogle Scholar
  15. Cassinelli G, Lanzi C, Pensa T, Gambetta RA, Nasini G, Cuccuru G, Cassinis M, Pratesi G, Polizzi D, Tortoreto M, Zunino F (2000) Clavilactones, a novel class of tyrosine kinase inhibitors of fungal origin. Biochem Pharmacol 59:1539–1547CrossRefPubMedGoogle Scholar
  16. Chang KL, Kung ML, Chow NH, Su SJ (2004) Genistein arrests hepatoma cells at G2/M phase: involvement of ATM activation and upregulation of p21waf1/cip1 and Wee1. Biochem Pharmacol 67:717–726CrossRefPubMedGoogle Scholar
  17. Chariot P, Bignani O (2003) Skeletal muscle disorders associated with selenium deficiency in humans. Muscle Nerve 27:662–668CrossRefPubMedGoogle Scholar
  18. Cheung WM, Hui WS, Chu PW, Chiu SW, Ip NY (2000) Ganoderma extract activates MAP kinases and induces the neuronal differentiation of rat pheochromocytoma PC12 cells. FEBS Lett 486:291–296CrossRefPubMedGoogle Scholar
  19. Cho JH, Cho SD, Hu H, Kim SH, Lee SK, Lee YS, Kang KS (2002) The roles of ERK1/2 and p38 MAP kinases in the preventive mechanisms of mushroom Phellinus linteus against the inhibition of gap junctional intercellular communication by hydrogen peroxide. Carcinogenesis 23:1163–1169CrossRefPubMedGoogle Scholar
  20. Choi YH, Lee WH, Park KY, Zhang L (2000) p53-Independent induction of p21waf1/cip1, reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells. Jpn J Cancer Res 91:164–173PubMedGoogle Scholar
  21. Chow LW, Lo CS, Loo WT, Hu XC, Sham JS (2003) Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and down-regulating cyclin D1 gene. Am J Chin Med 31:1–9Google Scholar
  22. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010–1014CrossRefPubMedGoogle Scholar
  23. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. J Am Med Assoc 276:1957–1963CrossRefGoogle Scholar
  24. Clark LC, Dalkin B, Krongrad A, Combs GF Jr, Turnbull BW, Slate EH, Witherington R, Herlong JH, Janosko E, Carpenter D, Borosso C, Falk S, Rounder J (1998) Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 81:730–734CrossRefPubMedGoogle Scholar
  25. Cleary JA, Kelly GE, Husband AJ (1999) The effect of molecular weight and beta-1,6-linkages on priming of macrophage function in mice by (1,3)-beta-d-glucan. Immun Cell Biol 77:395CrossRefGoogle Scholar
  26. Czop JK, Austen KF (1985) Properties of glycans that activate the human alternative complement pathway and interact with the human monocyte beta-glucan receptor. J Immunol 135:3388–3393Google Scholar
  27. De Silva V, Woznichak MM, Burns KL, Grant KB, May SW (2004) Selenium redox cycling in the protective effects of organoselenides against oxidant-induced DNA damage. J Am Chem Soc 126:2409–2413CrossRefPubMedGoogle Scholar
  28. Dernovics M, Stefanka Z, Fodor P (2002) Improving selenium extraction by sequential enzymatic processes for Se-speciation of selenium-enriched Agaricus bisporus. Anal Bioanal Chem 372:473–480CrossRefPubMedGoogle Scholar
  29. Didukh M, Wasser SP, Nevo E (2004) Impact of the family Agaricaceae (Fr.) Cohn on nutrition and medicine. Volz A (Ed.) ARG Ganter Verlag KG, Konigstein, GermanyGoogle Scholar
  30. Dong Y, Ganther HE, Stewart C, Ip C (2002) Identification of molecular targets associated with selenium-induced growth inhibition in human breast cells using cDNA microarrays. Cancer Res 62:708–714PubMedGoogle Scholar
  31. El-Bayoumy K, Narayanan BA, Desai DH, Narayanan NK, Pittman B, Amin SG, Schwartz J, Nixon DW (2003) Elucidation of molecular targets of mammary cancer chemoprevention in the rat by organoselenium compounds using cDNA microarray. Carcinogenesis 24:1505–1514CrossRefPubMedGoogle Scholar
  32. Erkel G, Anke T, Sterner O (1996) Inhibition of NF-kappa B activation by panepoxydone. Biochem Biophys Res Commun 226:214–221CrossRefPubMedGoogle Scholar
  33. Falch BH, Espevik T, Ryan L, Stokke BT (2000) The cytokine stimulating activity of (1→3)-beta-d-glucans is dependent on the triple helix conformation. Carbohydr Res 329:587–596CrossRefPubMedGoogle Scholar
  34. Fei P, Bernhard EJ, El-Deiry WS (2002) Tissue-specific induction of p53 targets in vivo. Cancer Res 62:7316–7327PubMedGoogle Scholar
  35. Fiala ES, Staretz ME, Pandya GA, El-Bayoumy K, Hamilton SR (1998) Inhibition of DNA cytosine methyltransferase by chemopreventive selenium compounds, determined by an improved assay for DNA cytosine methyltransferase and DNA cytosine methylation. Carcinogenesis 19:597–604CrossRefPubMedGoogle Scholar
  36. Fu M, Wang C, Zhang X, Pestell RG (2004) Signal transduction inhibitors in cellular function. Methods Mol Biol 284:15–36PubMedGoogle Scholar
  37. Fujimoto S, Furue H, Kimura T, Kondo T, Orita K, Taguchi T, Yoshida K, Ogawa N (1991) Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: a randomised controlled study. Eur J Cancer 27:1114–1118PubMedGoogle Scholar
  38. Furue H, Kitoh I (1981) Phase III study on Lentinan. Jpn J Cancer Chemother 8:944–960Google Scholar
  39. Gao Y, Zhou S (2002) The immunomodulating effects of Ganoderma lucidum. Int J Med Mushrooms 4:1–17Google Scholar
  40. Gasparian AV, Yao YJ, Lu J, Yemelyanov AY, Lyakh LA, Slaga TJ, Budunova IV (2002) Selenium compounds inhibit I kappa B kinase (IKK) and nuclear factor-kappa B (NF-kappa B) in prostate cancer cells. Mol Cancer Ther 1:1079–1087PubMedGoogle Scholar
  41. Gehrt A, Erkel G, Anke T, Sterner O (1998) Cycloepoxydon, 1-hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene and 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylbenzene, new inhibitors of eukaryotic signal transduction. J Antibiot 51:455–463PubMedGoogle Scholar
  42. Ghosh J (2004) Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase. Biochem Biophys Res Commun 315:624–635CrossRefPubMedGoogle Scholar
  43. Gingras D, Boivin D, Deckers C, Gendron S, Barthomeuf C, Beliveau R (2003) Neovastat—a novel antiangiogenic drug for cancer therapy. Anticancer Drugs 14:91–96CrossRefPubMedGoogle Scholar
  44. Gonindard C, Bergonzi C, Denier C, Sergheraert C, Klaebe A, Chavant L, Hollande E (1997) Synthetic hispidin, a PKC inhibitor, is more cytotoxic toward cancer cells than normal cells in vitro. Cell Biol Toxicol 13:141–153CrossRefPubMedGoogle Scholar
  45. Gopee NV, Johnson VJ, Sharma RP (2004) Sodium selenite-induced apoptosis in murine B-lymphoma cells is associated with inhibition of protein kinase C-{delta}, nuclear factor {kappa}B and inhibitor of apoptosis protein. Toxicol Sci 78:204–214CrossRefPubMedGoogle Scholar
  46. Graham DG, Tye RW, Vogel FS (1977) Inhibition of DNA polymerase from L1210 murine leukemia by a sulfhydryl reagent from Agaricus bisporus. Cancer Res 37:436–439PubMedGoogle Scholar
  47. Grube BJ, Eng ET, Kao YC, Kwon A, Chen S (2001) White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation. J Nutr 131:3288–3293PubMedGoogle Scholar
  48. Guns ES, Goldenberg SL, Brown PN (2002) Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol. Can J Urol 9:1684–1689PubMedGoogle Scholar
  49. Hayes AJ, Li LY, Lippman ME (1999) Science, medicine, and the future. Antivascular therapy: a new approach to cancer treatment. Br Med J 318:853–856Google Scholar
  50. Hickman ES, Helin K (2002) The regulation of APAF1 expression during development and tumorigenesis. Apoptosis 7:167–171CrossRefPubMedGoogle Scholar
  51. Hilger RA, Scheulen ME, Strumberg D (2002) The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie 25:511–518CrossRefPubMedGoogle Scholar
  52. Hirata N, Tsuzuki A, Ohno N, Saita M, Adachi Y, Yadomae T (1998) Cytokine synthesis of human monocytes stimulated by triple or single helical conformer of an antitumor (1→3)-beta-d-glucan preparation, sonifilan. Zentralbl Bakteriol 288:403–413PubMedGoogle Scholar
  53. Hobbs C (2001) Medicinal mushrooms: Modern clinical uses overview. Int J Med Mushrooms 3:86Google Scholar
  54. Holden JA (2001) DNA topoisomerases as anticancer drug targets: from the laboratory to the clinic. Curr Med Chem Anti-Cancer Agents 1:1–25Google Scholar
  55. Horiguchi Y, Kuroda K, Nakashima J, Murai M, Umezawa K (2003) Antitumor effect of a novel nuclear factor-kappa B activation inhibitor in bladder cancer cells. Expert Rev Anticancer Ther 3:793–798Google Scholar
  56. Hsieh TC, Kunicki J, Darzynkiewicz Z, Wu JM (2002a) Effects of extracts of Coriolus versicolor (I’m-Yunity) on cell-cycle progression and expression of interleukins-1 beta,-6, and -8 in promyelocytic HL-60 leukemic cells and mitogenically stimulated and nonstimulated human lymphocytes. J Altern Complement Med 8:591–602CrossRefPubMedGoogle Scholar
  57. Hsieh TC, Lu X, Yang QY, Chou WH, Wu JM (2002b) Changes in STAT1 and ERK by water and ethanol extracts of Im-Yunity (PSP) as mechanistic correlates of its clinical efficacy. Int Symp Predict Oncol Intervention Strategies 2002Google Scholar
  58. Hsieh TC, Wu JM (2001) Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells. Int J Oncol 18:81–88PubMedGoogle Scholar
  59. Hsu AL, Ching TT, Wang DS, Song X, Rangnekar VM, Chen CS (2000) The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem 275:11397–11403CrossRefPubMedGoogle Scholar
  60. Hu H, Ahn NS, Yang X, Lee YS, Kang KS (2002) Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF-7 human breast cancer cell. Int J Cancer 102:250–253CrossRefPubMedGoogle Scholar
  61. Hussain T, Gupta S, Mukhtar H (2003) Cyclooxygenase-2 and prostate carcinogenesis. Cancer Lett 191:125–135CrossRefPubMedGoogle Scholar
  62. Inoue A, Kodama N, Nanba H (2002) Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph node Th-1/Th-2 proportion. Biol Pharm Bull 25:536–540CrossRefPubMedGoogle Scholar
  63. Ishibashi K, Miura NN, Adachi Y, Ohno N, Yadomae T (2001) Relationship between solubility of grifolan, a fungal 1,3-beta-d-glucan, and production of tumor necrosis factor by macrophages in vitro. Biosci Biotechnol Biochem 65:1993–2000Google Scholar
  64. Jiang C, Ganther H, Lu J (2000) Monomethyl selenium-specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Mol Carcinogen 29:236–250CrossRefGoogle Scholar
  65. Jiang C, Wang Z, Ganther H, Lu J (2002) Distinct effects of methylseleninic acid versus selenite on apoptosis, cell cycle, and protein kinase pathways in DU145 human prostate cancer cells. Mol Cancer Ther 1:1059–1066PubMedGoogle Scholar
  66. Jin M, Jung HJ, Choi JJ, Jeon H, Oh JH, Kim B, Shin SS, Lee JK, Yoon K, Kim S (2003) Activation of selective transcription factors and cytokines by water-soluble extract from Lentinus lepideus. Exp Biol Med 228:749–758Google Scholar
  67. Jong S, Yang X (1999) PSP—a powerful biological response modifier from the mushroom Coriolous versicolor. In: Yang Q (ed) Advanced research in PSP. Hong Kong Association for Health Care, Hong Kong, pp 16–18Google Scholar
  68. Kalac P, Svoboda L (2000) A review of trace element concentrations in edible mushrooms. Food Chem 69:273–281CrossRefGoogle Scholar
  69. Kang J, Wang H-Q, Chen R-Y (2003) Studies on the constituents of the mycelia produced from fermented culture of Flammulina velutipes (W. Curt.:Fr.) Singer (Agaricomycetideae). Int J Med Mushroom 5:391–396CrossRefGoogle Scholar
  70. Kataoka K, Muta T, Yamazaki S, Takeshige K (2002) Activation of macrophages by linear (1→3)-beta-d-glucans. Implications for the recognition of fungi by innate immunity. J Biol Chem 277:36825–36831CrossRefPubMedGoogle Scholar
  71. Kawagishi H, Hamajima K, Inoue Y (2002) Novel hydroquinone as a matrix metallo-proteinase inhibitor from the mushroom, Piptoporus betulinus. Biosci Biotechnol Biochem 66:2748–2750CrossRefPubMedGoogle Scholar
  72. Kawagishi H, Li H, Tanno O, Inoue S, Ikeda S, Ohnishi-Kameyama M, Nagata T (1997) A lanostane-type triterpene from a mushroom Daedalea dickinsii. Phytochemistry 46:959–961CrossRefGoogle Scholar
  73. Kelner MJ, McMorris TC, Beck WT, Zamora JM, Taetle R (1987) Preclinical evaluation of illudins as anticancer agents. Cancer Res 47:3186–3189PubMedGoogle Scholar
  74. Kidd PM (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 5:4–26PubMedGoogle Scholar
  75. Kim DS, Jeong HJ, Bhat KP, Park SY, Kang SH, Yoo EH, Lee M, Lee HW, Krueger RJ, Kim DS (2000) Aromatase and sulfatase inhibitors from Lepiota americana. Planta Med 66:78–79CrossRefPubMedGoogle Scholar
  76. Kim KM, Kwon YG, Chung HT, Yun YG, Pae HO, Han JA, Ha KS, Kim TW, Kim YM (2003) Methanol extract of Cordyceps pruinosa inhibits in vitro and in vivo inflammatory mediators by suppressing NF-kappa B activation. Toxicol Appl Pharmacol 190:1–8Google Scholar
  77. Kimura Y, Taniguchi M, Baba K (2002) Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res 22:3309–3318PubMedGoogle Scholar
  78. Kimura Y, Tojima H, Fukase S, Takeda K (1994) Clinical evaluation of sizofilan as assistant immunotherapy in treatment of head and neck cancer. Acta Otolaryngol [Suppl] 511:192–195Google Scholar
  79. Kikuchi E, Horiguchi Y, Nakashima J, Kuroda K, Oya M, Ohigashi T, Takahashi N, Shima Y, Umezawa K, Murai M (2003) Suppression of hormone-refractory prostate cancer by a novel nuclear factor-kappa B inhibitor in nude mice. Cancer Res 63:107–110PubMedGoogle Scholar
  80. Kiremidjian-Schumacher L, Roy M, Glickman R, Schneider K, Rothstein S, Cooper J, Hochster H, Kim M, Newman R (2000) Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res 73:97–111CrossRefPubMedGoogle Scholar
  81. Kirschenbaum A, Liu X, Yao S, Levine AC (2001) The role of cyclooxygenase-2 in prostate cancer. Urology 58:127–131CrossRefPubMedGoogle Scholar
  82. Kleeff J, Kornmann M, Sawhney H, Korc M (2000) Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. Int J Cancer 86:399–407CrossRefPubMedGoogle Scholar
  83. Klein G, Vellenga E, Fraaije MW, Kamps WA, De Bont ES (2004) The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 50:87–100PubMedGoogle Scholar
  84. Kodama N, Komuta K, Sakai N, Nanba H (2002a) Effects of D-fraction, a polysaccharide from Grifola frondosa on tumor growth involve activation of NK cells. Biol Pharm Bull 25:1647–1650CrossRefPubMedGoogle Scholar
  85. Kodama N, Harada N, Nanba H (2002b) A polysaccharide, extract from Grifola frondosa, induces Th-1 dominant responses in carcinoma-bearing BALB/c mice. Jpn J Pharmacol 90:357–360CrossRefPubMedGoogle Scholar
  86. Kumar A, Takada Y, Boriek AM, Aggarwal BB (2004) Nuclear factor—kappa B: its role in health and disease. J Mol Med 82:434–448CrossRefPubMedGoogle Scholar
  87. Li Y, Mi C (2003) Proliferation inhibition and apoptosis onset in human ovarian carcinoma cell line SKOV3 induced by genistein. Ai Zheng 22:586–591PubMedGoogle Scholar
  88. Liebmann C (2001) Regulation of MAP kinase activity by peptide receptor signalling pathway: paradigms of multiplicity. Cell Signal 13:777–785CrossRefPubMedGoogle Scholar
  89. Lieberman R (2002) Chemoprevention of prostate cancer: Current status and future directions. Cancer Metastasis Rev 21:297–309Google Scholar
  90. Lipniacki T, Paszek P, Brasier AR, Luxon B, Kimmel M (2004) Mathematical model of NF-kappa B regulatory module. J Theor Biol 228:195–215CrossRefPubMedGoogle Scholar
  91. Lin SB, Li CH, Lee SS, Kan LS (2003) Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci 72:2381–2390CrossRefPubMedGoogle Scholar
  92. Liu F, Ooi VE, Fung MC (1999) Analysis of immunomodulating cytokine mRNAs in the mouse induced by mushroom polysaccharides. Life Sci 64:1005–1011CrossRefPubMedGoogle Scholar
  93. Lu J, Jiang C (2001) Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects. Nutr Cancer 40:64–73CrossRefPubMedGoogle Scholar
  94. Lu X, Guo J, Hsieh TC (2003) PC-SPES inhibits cell proliferation by modulating p21, cyclins D, E and B and multiple cell cycle-related genes in prostate cancer cells. Cell Cycle 2:59–63PubMedGoogle Scholar
  95. Lucas EH, Byerrum M, Clarke DA, Reilly HC, Stevens JA, Stock CC (1958) Production of oncostatic principles in vivo and in vitro by species of the genus Calvatia. Antibiot Annu 6:493-496Google Scholar
  96. Lucas EH, Montesano R, Pepper MS, Hafner M, Sablon E (1957) Tumor inhibitors in Boletus edulis and other holobasidiomycetes. Antibiot Chemother 7:1–4Google Scholar
  97. Masamura S, Adlercreutz H, Harvey H, Lipton A, Demers LM, Santen RJ, Santner SJ (1995) Aromatase inhibitor development for treatment of breast cancer. Breast Cancer Res Treat 33:19–26PubMedGoogle Scholar
  98. Matsui H, Suzuka K, Iitsuka Y, Yamazawa K, Tanaka N, Mitsuhashi A, Seki K, Sekiya S (2002) Salvage combination chemotherapy with 5-fluorouracil and actinomycin D for patients with refractory, high-risk gestational trophoblastic tumors. Cancer 95:1051–1054CrossRefPubMedGoogle Scholar
  99. Matsumoto N, Ariga A, To-e S Nakamura H, Agata N, Hirano S, Inoue J, Umezawa K (2000) Synthesis of NF-kappa B activation inhibitors derived from epoxyquinomicin C. Bioorg Med Chem Lett 10:865–869CrossRefPubMedGoogle Scholar
  100. McMorris TC, Elayadi AN, Yu J, Kelner MJ (1999) Metabolism of antitumor acylfulvene by rat liver cytosol. Biochem Pharmacol 57:83–88CrossRefPubMedGoogle Scholar
  101. McMorris TC, Kelner MJ, Wang W, Diaz MA, Estes LA, Taetle R (1996a) Acylfulvenes, a new class of potent antitumor agents. Experientia 52:75–80PubMedGoogle Scholar
  102. McMorris TC, Kelner MJ, Wang W, Moon S, Taetle R (1990) On the mechanism of toxicity of illudins: the role of glutathione. Chem Res Toxicol 3:574–579PubMedGoogle Scholar
  103. McMorris TC, Kelner MJ, Wang W, Yu J, Estes LA, Taetle R (1996b) (Hydroxymethyl)acylfulvene: an illudin derivative with superior antitumor properties. J Nat Prod 59:896–899CrossRefPubMedGoogle Scholar
  104. McMorris TC, Staake M, Kelner MJ (2004) Synthesis and biological activity of enantiomers of antitumor irofulven. J Org Chem 69:619–623CrossRefPubMedGoogle Scholar
  105. Michelot D, Siobud E, Dore J, Viel C, Poirier F (1998) Update of metal content profiles in mushrooms—toxicological implications and tentative approach to the mechanisms of bioaccumulation. Toxicon 36:1997–2012CrossRefPubMedGoogle Scholar
  106. Miura S, Izuta S (2004) DNA polymerases as targets of anticancer nucleosides. Curr Drug Targets 5:191–195PubMedGoogle Scholar
  107. Mizuno T (1995a) Bioactive biomolecules of mushrooms: food function and medicinal effect of mushroom fungi. Food Rev Int 11:7–21Google Scholar
  108. Mizuno T (1995b) Yamabushitake, Hericium erinaceum: bioactive substances and medicinal utilization. Food Rev Int 11:173–178Google Scholar
  109. Mizuno T (1999) The extraction and development of antitumor-active polysaccharides from medicinal mushrooms in Japan. Int J Med Mushrooms 1:9–29Google Scholar
  110. Mizushina Y, Akihisa T, Ukiya M, Murakami C, Kuriyama I, Xu X, Yoshida H, Sakaguchi K (2004) A novel DNA topoisomerase inhibitor: dehydroebriconic acid, one of the lanostane-type triterpene acids from Poria cocos. Cancer Sci 95:354–360PubMedGoogle Scholar
  111. Mizushina Y, Hanashima L, Yamaguchi T, Takemura M, Sugawara F, Saneyoshi M, Matsukage A, Yoshida S, Sakaguchi K (1998a) A mushroom fruiting body-inducing substance inhibits activities of replicative DNA polymerases. Biochem Biophys Res Commun 249:17–22CrossRefPubMedGoogle Scholar
  112. Mizushina Y, Iida A, Ohta K, Sugawara F, Sakaguchi K (2000) Novel triterpenoids inhibit both DNA polymerase and DNA topoisomerase. Biochem J 350:757–763CrossRefPubMedGoogle Scholar
  113. Mizushina Y, Takahashi N, Hanashima L, Koshino H, Esumi Y, Uzawa J, Sugawara F, Sakaguchi K (1999) Lucidenic acid O and lactone, new terpene inhibitors of eukaryotic DNA polymerases from a basidiomycete, Ganoderma lucidum. Bioorg Med Chem 7:2047–2052CrossRefPubMedGoogle Scholar
  114. Mizushina Y, Tanaka N, Kitamura A, Tamai K, Ikeda M, Takemura M, Sugawara F, Arai T, Matsukage A, Yoshida S, Sakaguchi K (1998b) The inhibitory effect of novel triterpenoid compounds, fomitellic acids, on DNA polymerase beta. Biochem J 330:1325–1332PubMedGoogle Scholar
  115. Mueller A, Raptis J, Rice PJ, Kalbfleisch JH, Stout RD, Ensley HE, Browder W, Williams DL (2000) The influence of glucan polymer structure and solution conformation on binding to (1→3)-beta-d-glucan receptors in a human monocyte-like cell line. Glycobiology 10:339–346CrossRefPubMedGoogle Scholar
  116. Nanba H, Mori K, Toyomasu T, Kuroda H (1987) Antitumor action of shiitake (Lentinus edodes) fruit-bodies orally administered to mice. Chem Pharm Bull 35:2453–2458PubMedGoogle Scholar
  117. Nasta SD, Hoff PM, George CS, Neubauer M, Cohen SC, Abbruzzese J, Winn R, Pazdur RM (2003) Phase II study of MGI-114 administered intravenously for 5 days every 28 days to patients with metastatic colorectal cancer. Am J Clin Oncol 26:132–134CrossRefPubMedGoogle Scholar
  118. Okazaki M, Adachi Y, Ohno N, Yadomae T (1995) Structure–activity relationship of (1→3)-beta-d-glucans in the induction of cytokine production from macrophages, in vitro. Biol Pharm Bull 18:1320–1327PubMedGoogle Scholar
  119. Ooi VE, Liu F (2000) Immunomodulation and anticancer activity of polysaccharide–protein complexes. Curr Med Chem 7:715–729PubMedGoogle Scholar
  120. Oren M (1999) Regulation of the p53 tumor suppressor protein. J Biol Chem 274:36031–36034CrossRefPubMedGoogle Scholar
  121. Pahl HL, Krauss B, Schulze-Osthoff K, Decker T, Traenckner EB, Vogt M, Myers C, Parks T, Warring P, Muhlbacher A, Czernilofsky AP, Baeuerle PA (1996) The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappa B. J Exp Med 183:1829–1840CrossRefPubMedGoogle Scholar
  122. Park IH, Jeon SY, Lee HJ, Kim SI, Song KS (2004) A beta-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus. Planta Med 70:143–146CrossRefPubMedGoogle Scholar
  123. Peterson G, Barnes S (1993) Genistein and biochanin A inhibit the growth of human prostate cancer cells but not epidermal growth factor receptor tyrosine autophosphorylation. Prostate 22:335–345PubMedGoogle Scholar
  124. Peterson G, Barnes S (1996) Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ 7:1345–1351PubMedGoogle Scholar
  125. Pierson AS, Gibbs P, Richards J, Russ P, Eckhardt SG, Gonzalez R (2002) A phase II study of Irofulven (MGI 114) in patients with stage IV melanoma. Invest New Drugs 20:357–362CrossRefPubMedGoogle Scholar
  126. Poindessous V, Koeppel F, Raymond E, Comisso M, Waters SJ, Larsen AK (2003b) Marked activity of irofulven toward human carcinoma cells: comparison with cisplatin and ecteinascidin. Clin Cancer Res 9:2817–2825Google Scholar
  127. Poindessous V, Koeppel F, Raymond E, Cvitkovic E, Waters SJ, Larsen AK (2003a) Enhanced antitumor activity of irofulven in combination with 5-fluorouracil and cisplatin in human colon and ovarian carcinoma cells. Int J Oncol 23:1347–1355PubMedGoogle Scholar
  128. Raich PC, Lu J, Thompson HJ, Combs GF Jr (2001) Selenium in cancer prevention: clinical issues and implications. Cancer Invest 19:540–553CrossRefPubMedGoogle Scholar
  129. Rao A, Coan A, Welsh JE, Barclay WW, Koumenis C, Cramer SD (2004) Vitamin D receptor and p21/WAF1 are targets of genistein and 1,25-dihydroxyvitamin D3 in human prostate cancer cells. Cancer Res 64:2143–2147PubMedGoogle Scholar
  130. Ravi R, Bedi A (2004) NF-kappa B in cancer-a friend turned foe. Drug Resist Update 7:53–67CrossRefGoogle Scholar
  131. Rayman MP, Rayman MP (2002) The argument for increasing selenium intake. Proc Nutr Soc 61:203–215CrossRefPubMedGoogle Scholar
  132. Rees BJ, Ye JL (1999) Pyrrhoglossum and the small-spored species of Gymnopilus (Cortinariaceae) in eastern Australia. Aust Syst Bot 12:255–270Google Scholar
  133. Ross GD, Vetvicka V, Yan J, Xia Y, Vetvickova J (1999) Therapeutic intervention with complement and beta-glucan in cancer. Immunopharmacology 42:61–74Google Scholar
  134. Safir N, Wendel A, Saile R, Chabraoui L (2003) The effect of selenium on immune functions of J774.1 cells. Clin Chem Lab Med 41:1005–1011Google Scholar
  135. Sakagami H, Sugaya K, Utsumi A, Fujinaga S, Sato T, Takeda M (1993) Stimulation by PSK of interleukin-1 production by human peripheral blood mononuclear cells. Anticancer Res 13:671–675PubMedGoogle Scholar
  136. Sakagami Y, Mizoguchi Y, Shin T, Seki S, Kobayashi K, Morisawa S, Yamamoto S (1988) Effects of an anti-tumor polysaccharide, schizophyllan, on interferon-gamma and interleukin 2 production by peripheral blood mononuclear cells. Biochem Biophys Res Commun 155:650–655PubMedGoogle Scholar
  137. Scappaticci FA (2002) Mechanisms and future directions for angiogenesis-based cancer therapies. J Clin Oncol 20:3906–3927CrossRefPubMedGoogle Scholar
  138. Schilder RJ, Blessing JA, Pearl ML, Rose PG (2004) Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: a phase II study of the Gynecologic oncology group. Invest New Drugs 22:343–349CrossRefPubMedGoogle Scholar
  139. Shah DT, Larsen B (1991) Clinical isolates of yeast produce a gliotoxin-like substance. Mycopathologia 116:203–208PubMedGoogle Scholar
  140. Sherman CA, Herndon JE 2nd, Watson DM, Green MR (2004) A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with relapsed or refractory non-small cell lung cancer. Lung Cancer 45:387–392CrossRefPubMedGoogle Scholar
  141. Silberborth S, Erkel G, Anke T, Sterner O (2000) The irpexans, a new group of biologically active metabolites produced by the basidiomycete Irpex sp. 93028. J Antibiot 53:1137–1144PubMedGoogle Scholar
  142. Silberborth S, Stumpf A, Erkel G, Anke T, Sterner O (2002) Gerronemins A-F, cytotoxic biscatechols from a Gerronema species. Phytochemistry 59:643–648CrossRefPubMedGoogle Scholar
  143. Sinha R, El-Bayoumy K (2004) Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds. Curr Cancer Drug Targets 4:13–28PubMedGoogle Scholar
  144. Slejkovec Z, van Elteren JT, Woroniecka UD, Kroon KJ, Falnoga I, Byrne AR (2000) Preliminary study on the determination of selenium compounds in some selenium-accumulating mushrooms. Biol Trace Elem Res 75:139–155CrossRefPubMedGoogle Scholar
  145. Sliva D (2003) Ganoderma lucidum (reishi) in cancer treatment. Integr Cancer Ther 2:358–364Google Scholar
  146. Sliva D, Labarrere C, Slivova V, Sedlak M, Lloyd FP Jr, Ho NW (2002) Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells. Biochem Biophys Res Commun 298:603–612CrossRefPubMedGoogle Scholar
  147. Sliva D, Sedlak M, Slivova V, Valachovicova T, Lloyd FP Jr, Ho NW (2003) Biologic activity of spores and dried powder from Ganoderma lucidum for the inhibition of highly invasive human breast and prostate cancer cells. J Altern Complement Med 9:491–497CrossRefPubMedGoogle Scholar
  148. Song YS, Kim SH, Sa JH, Jin C, Lim CJ, Park EH (2003) Anti-angiogenic, antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus. J Ethnopharmacol 88:113–116CrossRefPubMedGoogle Scholar
  149. Soussi T (2000) The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann NY Acad Sci 910:121–139PubMedGoogle Scholar
  150. Spolar MR, Schaffer EM, Beelman RB, Milner JA (1999) Selenium-enriched Agaricus bisporus mushrooms suppress 7,12-dimethlybenz[a]anthracene bioactivation in mammary tissue. Cancer Lett 138:145–150CrossRefPubMedGoogle Scholar
  151. Stajic M, Milenkovic I, Brceski I, Vukojevic J, Duletic-Lausevic S (2002) Mycelial growth of edible and medicinal oyster mushroom [Pleurotus ostreatus (Jacq.: Fr.) Kumm.] on selenium-enriched media. Int J Med Mushrooms 4:62–66Google Scholar
  152. Taguchi T, Furue H, Kimura T, Kondo T, Hattori T, Itoh T, Osawa N (1985) End-point results of phase III study of lentinan. Jpn J Cancer Chemother 12:366–380Google Scholar
  153. Takaku T, Kimura Y, Okuda H (2001) Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action. J Nutr 131:1409–1413PubMedGoogle Scholar
  154. Taketo MM (1998a) Cyclooxygenase-2 inhibitors in tumorigenesis (part I). J Natl Cancer Inst 90:1529–1536Google Scholar
  155. Taketo MM (1998b) Cyclooxygenase-2 inhibitors in tumorigenesis (part II). J Natl Cancer Inst 90:1609–1620Google Scholar
  156. Tanaka N, Kitamura A, Mizushina Y, Sugawara F, Sakaguchi K (1998) Fomitellic acids, triterpenoid inhibitors of eukaryotic DNA polymerases from a basidiomycete, Fomitella fraxinea. J Nat Prod 61:193–197Google Scholar
  157. Topcu Z (2001) DNA topoisomerases as targets for anticancer drugs. J Clin Pharm Ther 26:405–416CrossRefPubMedGoogle Scholar
  158. Tzianabos AO (2000) Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev 13:523–533CrossRefPubMedGoogle Scholar
  159. Van Laar ES, Roth S, Weitman S, MacDonald JR, Waters SJ (2004) Activity of irofulven against human pancreatic carcinoma cell lines in vitro and in vivo. Anticancer Res 24:59–65PubMedGoogle Scholar
  160. Venkateswaran V, Klotz LH, Fleshner NE (2002) Selenium modulation of cell proliferation and cell cycle biomarkers in human prostate carcinoma cell lines. Cancer Res 62:2540–2545PubMedGoogle Scholar
  161. Vetvicka V, Thornton BP, Wieman TJ, Ross GD (1997) Targeting of NK cells to mammary carcinoma via naturally occurring tumor cellbound iC3b and beta-glucan-primed CR3 (CD11b/CD18). J Immunol 159:599–605Google Scholar
  162. Vigushin DM, Mirsaidi N, Brooke G, Sun C, Pace P, Inman L, Moody CJ, Coombes RC (2004) Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. Med Oncol 21:21–30CrossRefPubMedGoogle Scholar
  163. Wada T, Penninger JM (2004) Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23:2838–2849CrossRefPubMedGoogle Scholar
  164. Wang W, Waters SJ, MacDonald JR, Roth C, Shentu S, Freeman J, Von Hoff DD, Miller AR (2002) Irofulven (6-hydroxymethylacylfulvene, MGI 114)-induced apoptosis in human pancreatic cancer cells is mediated by ERK and JNK kinases. Anticancer Res 22:559–564PubMedGoogle Scholar
  165. Waring P, Eichner RD, Tiwari-Palni U, Mullbacher A (1987) Gliotoxin-E: a new biologically active epipolythidioxopiperazine isolated from Penicillium terlikowskii. Aust J Chem 40:991–997Google Scholar
  166. Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60:258–274Google Scholar
  167. Wasser SP, Weis AL (1999) Medicinal properties of substances occurring in higher basidiomycetes mushrooms: current perspectives (review). Int J Med Mushrooms 1:31–62Google Scholar
  168. Watanabe A, Kamei K, Sekine T, Waku M, Nishimura K, Miyaji M, Tatsumi K, Kuriyama T (2004) Effect of aeration on gliotoxin production by Aspergillus fumigatus in its culture filtrate. Mycopathologia 157:19–27CrossRefPubMedGoogle Scholar
  169. Werner AR, Beelman RB (2002) Growing high-selenium edible and medicinal button mushrooms (Agaricus bisporus (J. Lge) Imbach) as ingredients for functional foods or dietary supplements. Int J Med Mushrooms 4:88–94Google Scholar
  170. Xia Y, Vetvicka V, Yan J, Hanikyrova M, Mayadas T, Ross GD (1999) The beta-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J Immunol 162:2281–2290Google Scholar
  171. Yamamoto Y, Gaynor RB (2004) I kappa B kinases: key regulators of the NF-kappa B pathway. Trends Biochem Sci 29:72–79CrossRefPubMedGoogle Scholar
  172. Yan J, Vetvicka V, Xia Y, Coxon A, Carroll MC, Mayadas TN, Ross GD (1999) Beta-glucan, a “specific” biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol 163:3045–3052Google Scholar
  173. Yang W (1999) History, present status and perspectives of the study of yumzhi polysaccharides. In: Yang Q (ed) Advanced research in PSP. Hong Kong Association for Health Care, Hong Kong, pp 5–15Google Scholar
  174. Yao W (1999) Prospective randomised trial of radiotherapy plus PSP in the treatment of oesophageal carcinoma. In: Yang Q (ed) Advanced research in PSP. Hong Kong Association for Health Care, Hong Kong, pp 310–313Google Scholar
  175. Yoo HS, Shin JW, Cho JH, Son CG, Lee YW, Park SY, Cho CK (2004) Effects of Cordyceps militaris extract on angiogenesis and tumor growth. Acta Pharmacol Sin 25:657–665Google Scholar
  176. Yoshiji H, Kuriyama S, Ways DK, Yoshii J, Miyamoto Y, Kawata M, Ikenaka Y, Tsujinoue H, Nakatani T, Shibuya M, Fukui H (1999) Protein kinase C lies on the signaling pathway for vascular endothelial growth factor-mediated tumor development and angiogenesis. Cancer Res 59:4413–4418PubMedGoogle Scholar
  177. Zhang Y, Mills GL, Nair MG (2002) Cyclooxygenase inhibitory and antioxidant compounds from the mycelia of the edible mushroom Grifola frondosa. J Agric Food Chem 50:7581–7585CrossRefPubMedGoogle Scholar
  178. Zhong W, Oberley TD (2001) Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer Res 61:7071–7078PubMedGoogle Scholar
  179. Zhuang C, Wasser SP (2004) Medicinal value of culinary-medicinal Maitake mushroom Grifola frondosa (Dicks.:Fr.) S. F. Gray (Aphyllophoromycetideae). Review. Int J Med Mushrooms 6:287-314Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ben-Zion Zaidman
    • 1
    • 2
  • Majed Yassin
    • 1
    • 2
  • Jamal Mahajna
    • 2
  • Solomon P. Wasser
    • 1
  1. 1.Biodiversity and Biotechnology Center of Cryptogamic Plants and Fungi, The Institute of EvolutionUniversity of HaifaHaifaIsrael
  2. 2.Migal–Galilee Technology CenterKiryat ShmonaIsrael

Personalised recommendations