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Medicinal mushroom modulators of molecular targets as cancer therapeutics

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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.

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References

  • 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 72:4159–4171

    Article  CAS  PubMed  Google Scholar 

  • 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 17:1554–1560

    CAS  PubMed  Google Scholar 

  • 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 9:263–273

    CAS  PubMed  Google Scholar 

  • 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 68:448–450

    Article  CAS  PubMed  Google Scholar 

  • Anonymous (2003) Development of Flammulina velutipes with anticancer function. RDA E-Newsl 2

  • 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 277:24625–24630

    Article  CAS  PubMed  Google Scholar 

  • Awadh Ali NA, Mothana RA, Lesnau A, Pilgrim H, Lindequist U (2003) Antiviral activity of Inonotus hispidus. Fitoterapia 74:483–485

    Article  CAS  PubMed  Google Scholar 

  • 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 249:499–504

    Article  CAS  PubMed  Google Scholar 

  • Beecken WD, Kramer W, Jonas D (2000) New molecular mediators in tumor angiogenesis. J Cell Mol Med 4:262–269

    CAS  PubMed  Google Scholar 

  • 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 19:317–320

    Article  CAS  PubMed  Google Scholar 

  • Berns H, Humar R, Hengerer B, Kiefer FN, Battegay EJ (2000) RACK1 is up-regulated in angiogenesis and human carcinomas. FASEB J 14:2549–2558

    Article  CAS  PubMed  Google Scholar 

  • Borchers AT, Stern JS, Hackman RM, Keen CL, Gershwin ME (1999) Mushrooms, tumors, and immunity. Proc Soc Exp Biol Med 221:281–293

    Article  CAS  PubMed  Google Scholar 

  • 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 197:1119–1124

    Article  CAS  PubMed  Google Scholar 

  • Burk RF (2002) Selenium, an antioxidant nutrient. Nutr Clin Care 5:75–79

    Article  PubMed  Google Scholar 

  • 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 59:1539–1547

    Article  CAS  PubMed  Google Scholar 

  • 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 67:717–726

    Article  CAS  PubMed  Google Scholar 

  • Chariot P, Bignani O (2003) Skeletal muscle disorders associated with selenium deficiency in humans. Muscle Nerve 27:662–668

    Article  CAS  PubMed  Google Scholar 

  • 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 486:291–296

    Article  CAS  PubMed  Google Scholar 

  • 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 23:1163–1169

    Article  CAS  PubMed  Google Scholar 

  • 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 91:164–173

    CAS  PubMed  Google Scholar 

  • 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 31:1–9

    Google Scholar 

  • 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 303:1010–1014

    Article  CAS  PubMed  Google Scholar 

  • 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 276:1957–1963

    Article  CAS  Google Scholar 

  • 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 81:730–734

    Article  CAS  PubMed  Google Scholar 

  • 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 77:395

    Article  CAS  Google Scholar 

  • 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 135:3388–3393

    Google Scholar 

  • 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 126:2409–2413

    Article  PubMed  Google Scholar 

  • 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 372:473–480

    Article  CAS  PubMed  Google Scholar 

  • 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, Germany

  • 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 62:708–714

    CAS  PubMed  Google Scholar 

  • 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 24:1505–1514

    Article  CAS  PubMed  Google Scholar 

  • Erkel G, Anke T, Sterner O (1996) Inhibition of NF-kappa B activation by panepoxydone. Biochem Biophys Res Commun 226:214–221

    Article  CAS  PubMed  Google Scholar 

  • 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 329:587–596

    Article  CAS  PubMed  Google Scholar 

  • Fei P, Bernhard EJ, El-Deiry WS (2002) Tissue-specific induction of p53 targets in vivo. Cancer Res 62:7316–7327

    CAS  PubMed  Google Scholar 

  • 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 19:597–604

    Article  CAS  PubMed  Google Scholar 

  • Fu M, Wang C, Zhang X, Pestell RG (2004) Signal transduction inhibitors in cellular function. Methods Mol Biol 284:15–36

    CAS  PubMed  Google Scholar 

  • 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 27:1114–1118

    CAS  PubMed  Google Scholar 

  • Furue H, Kitoh I (1981) Phase III study on Lentinan. Jpn J Cancer Chemother 8:944–960

    Google Scholar 

  • Gao Y, Zhou S (2002) The immunomodulating effects of Ganoderma lucidum. Int J Med Mushrooms 4:1–17

    Google Scholar 

  • 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 1:1079–1087

    CAS  PubMed  Google Scholar 

  • 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 51:455–463

    CAS  PubMed  Google Scholar 

  • Ghosh J (2004) Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by metabolites of arachidonate 5-lipoxygenase. Biochem Biophys Res Commun 315:624–635

    Article  CAS  PubMed  Google Scholar 

  • Gingras D, Boivin D, Deckers C, Gendron S, Barthomeuf C, Beliveau R (2003) Neovastat—a novel antiangiogenic drug for cancer therapy. Anticancer Drugs 14:91–96

    Article  CAS  PubMed  Google Scholar 

  • 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 13:141–153

    Article  CAS  PubMed  Google Scholar 

  • 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 78:204–214

    Article  CAS  PubMed  Google Scholar 

  • Graham DG, Tye RW, Vogel FS (1977) Inhibition of DNA polymerase from L1210 murine leukemia by a sulfhydryl reagent from Agaricus bisporus. Cancer Res 37:436–439

    CAS  PubMed  Google Scholar 

  • 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 131:3288–3293

    CAS  PubMed  Google Scholar 

  • Guns ES, Goldenberg SL, Brown PN (2002) Mass spectral analysis of PC-SPES confirms the presence of diethylstilbestrol. Can J Urol 9:1684–1689

    CAS  PubMed  Google Scholar 

  • Hayes AJ, Li LY, Lippman ME (1999) Science, medicine, and the future. Antivascular therapy: a new approach to cancer treatment. Br Med J 318:853–856

    CAS  Google Scholar 

  • Hickman ES, Helin K (2002) The regulation of APAF1 expression during development and tumorigenesis. Apoptosis 7:167–171

    Article  CAS  PubMed  Google Scholar 

  • Hilger RA, Scheulen ME, Strumberg D (2002) The Ras-Raf-MEK-ERK pathway in the treatment of cancer. Onkologie 25:511–518

    Article  CAS  PubMed  Google Scholar 

  • 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 288:403–413

    CAS  PubMed  Google Scholar 

  • Hobbs C (2001) Medicinal mushrooms: Modern clinical uses overview. Int J Med Mushrooms 3:86

    Google Scholar 

  • Holden JA (2001) DNA topoisomerases as anticancer drug targets: from the laboratory to the clinic. Curr Med Chem Anti-Cancer Agents 1:1–25

    Google Scholar 

  • 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 3:793–798

    Google Scholar 

  • 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 8:591–602

    Article  PubMed  Google Scholar 

  • 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 2002

  • 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 18:81–88

    CAS  PubMed  Google Scholar 

  • 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 275:11397–11403

    Article  CAS  PubMed  Google Scholar 

  • 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 102:250–253

    Article  CAS  PubMed  Google Scholar 

  • Hussain T, Gupta S, Mukhtar H (2003) Cyclooxygenase-2 and prostate carcinogenesis. Cancer Lett 191:125–135

    Article  CAS  PubMed  Google Scholar 

  • 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 25:536–540

    Article  CAS  PubMed  Google Scholar 

  • 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 65:1993–2000

    Google Scholar 

  • Jiang C, Ganther H, Lu J (2000) Monomethyl selenium-specific inhibition of MMP-2 and VEGF expression: implications for angiogenic switch regulation. Mol Carcinogen 29:236–250

    Article  CAS  Google Scholar 

  • 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 1:1059–1066

    CAS  PubMed  Google Scholar 

  • 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 228:749–758

    CAS  Google Scholar 

  • 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 16–18

    Google Scholar 

  • Kalac P, Svoboda L (2000) A review of trace element concentrations in edible mushrooms. Food Chem 69:273–281

    Article  CAS  Google Scholar 

  • 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 5:391–396

    Article  CAS  Google Scholar 

  • 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 277:36825–36831

    Article  CAS  PubMed  Google Scholar 

  • Kawagishi H, Hamajima K, Inoue Y (2002) Novel hydroquinone as a matrix metallo-proteinase inhibitor from the mushroom, Piptoporus betulinus. Biosci Biotechnol Biochem 66:2748–2750

    Article  CAS  PubMed  Google Scholar 

  • 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 46:959–961

    Article  Google Scholar 

  • Kelner MJ, McMorris TC, Beck WT, Zamora JM, Taetle R (1987) Preclinical evaluation of illudins as anticancer agents. Cancer Res 47:3186–3189

    CAS  PubMed  Google Scholar 

  • Kidd PM (2000) The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 5:4–26

    CAS  PubMed  Google Scholar 

  • 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 66:78–79

    Article  CAS  PubMed  Google Scholar 

  • 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 190:1–8

    Google Scholar 

  • 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 22:3309–3318

    CAS  PubMed  Google Scholar 

  • 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] 511:192–195

    CAS  Google Scholar 

  • 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 63:107–110

    CAS  PubMed  Google Scholar 

  • 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 73:97–111

    Article  CAS  PubMed  Google Scholar 

  • Kirschenbaum A, Liu X, Yao S, Levine AC (2001) The role of cyclooxygenase-2 in prostate cancer. Urology 58:127–131

    Article  CAS  PubMed  Google Scholar 

  • Kleeff J, Kornmann M, Sawhney H, Korc M (2000) Actinomycin D induces apoptosis and inhibits growth of pancreatic cancer cells. Int J Cancer 86:399–407

    Article  CAS  PubMed  Google Scholar 

  • 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 50:87–100

    CAS  PubMed  Google Scholar 

  • 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 25:1647–1650

    Article  CAS  PubMed  Google Scholar 

  • 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 90:357–360

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Takada Y, Boriek AM, Aggarwal BB (2004) Nuclear factor—kappa B: its role in health and disease. J Mol Med 82:434–448

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Mi C (2003) Proliferation inhibition and apoptosis onset in human ovarian carcinoma cell line SKOV3 induced by genistein. Ai Zheng 22:586–591

    PubMed  Google Scholar 

  • Liebmann C (2001) Regulation of MAP kinase activity by peptide receptor signalling pathway: paradigms of multiplicity. Cell Signal 13:777–785

    Article  CAS  PubMed  Google Scholar 

  • Lieberman R (2002) Chemoprevention of prostate cancer: Current status and future directions. Cancer Metastasis Rev 21:297–309

    Google Scholar 

  • Lipniacki T, Paszek P, Brasier AR, Luxon B, Kimmel M (2004) Mathematical model of NF-kappa B regulatory module. J Theor Biol 228:195–215

    Article  CAS  PubMed  Google Scholar 

  • 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 72:2381–2390

    Article  CAS  PubMed  Google Scholar 

  • Liu F, Ooi VE, Fung MC (1999) Analysis of immunomodulating cytokine mRNAs in the mouse induced by mushroom polysaccharides. Life Sci 64:1005–1011

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Jiang C (2001) Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects. Nutr Cancer 40:64–73

    Article  CAS  PubMed  Google Scholar 

  • 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 2:59–63

    CAS  PubMed  Google Scholar 

  • 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 6:493-496

    Google Scholar 

  • Lucas EH, Montesano R, Pepper MS, Hafner M, Sablon E (1957) Tumor inhibitors in Boletus edulis and other holobasidiomycetes. Antibiot Chemother 7:1–4

    Google Scholar 

  • 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 33:19–26

    CAS  PubMed  Google Scholar 

  • 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 95:1051–1054

    Article  CAS  PubMed  Google Scholar 

  • 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 10:865–869

    Article  CAS  PubMed  Google Scholar 

  • McMorris TC, Elayadi AN, Yu J, Kelner MJ (1999) Metabolism of antitumor acylfulvene by rat liver cytosol. Biochem Pharmacol 57:83–88

    Article  CAS  PubMed  Google Scholar 

  • McMorris TC, Kelner MJ, Wang W, Diaz MA, Estes LA, Taetle R (1996a) Acylfulvenes, a new class of potent antitumor agents. Experientia 52:75–80

    CAS  PubMed  Google Scholar 

  • 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 3:574–579

    CAS  PubMed  Google Scholar 

  • 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 59:896–899

    Article  CAS  PubMed  Google Scholar 

  • McMorris TC, Staake M, Kelner MJ (2004) Synthesis and biological activity of enantiomers of antitumor irofulven. J Org Chem 69:619–623

    Article  CAS  PubMed  Google Scholar 

  • 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 36:1997–2012

    Article  CAS  PubMed  Google Scholar 

  • Miura S, Izuta S (2004) DNA polymerases as targets of anticancer nucleosides. Curr Drug Targets 5:191–195

    CAS  PubMed  Google Scholar 

  • Mizuno T (1995a) Bioactive biomolecules of mushrooms: food function and medicinal effect of mushroom fungi. Food Rev Int 11:7–21

    CAS  Google Scholar 

  • Mizuno T (1995b) Yamabushitake, Hericium erinaceum: bioactive substances and medicinal utilization. Food Rev Int 11:173–178

    CAS  Google Scholar 

  • Mizuno T (1999) The extraction and development of antitumor-active polysaccharides from medicinal mushrooms in Japan. Int J Med Mushrooms 1:9–29

    CAS  Google Scholar 

  • 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 95:354–360

    CAS  PubMed  Google Scholar 

  • 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 249:17–22

    Article  CAS  PubMed  Google Scholar 

  • Mizushina Y, Iida A, Ohta K, Sugawara F, Sakaguchi K (2000) Novel triterpenoids inhibit both DNA polymerase and DNA topoisomerase. Biochem J 350:757–763

    Article  CAS  PubMed  Google Scholar 

  • 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 7:2047–2052

    Article  CAS  PubMed  Google Scholar 

  • 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 330:1325–1332

    CAS  PubMed  Google Scholar 

  • 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 10:339–346

    Article  CAS  PubMed  Google Scholar 

  • Nanba H, Mori K, Toyomasu T, Kuroda H (1987) Antitumor action of shiitake (Lentinus edodes) fruit-bodies orally administered to mice. Chem Pharm Bull 35:2453–2458

    CAS  PubMed  Google Scholar 

  • 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 26:132–134

    Article  CAS  PubMed  Google Scholar 

  • 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 18:1320–1327

    CAS  PubMed  Google Scholar 

  • Ooi VE, Liu F (2000) Immunomodulation and anticancer activity of polysaccharide–protein complexes. Curr Med Chem 7:715–729

    CAS  PubMed  Google Scholar 

  • Oren M (1999) Regulation of the p53 tumor suppressor protein. J Biol Chem 274:36031–36034

    Article  CAS  PubMed  Google Scholar 

  • 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 183:1829–1840

    Article  CAS  PubMed  Google Scholar 

  • 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 70:143–146

    Article  CAS  PubMed  Google Scholar 

  • 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 22:335–345

    CAS  PubMed  Google Scholar 

  • Peterson G, Barnes S (1996) Genistein inhibits both estrogen and growth factor-stimulated proliferation of human breast cancer cells. Cell Growth Differ 7:1345–1351

    CAS  PubMed  Google Scholar 

  • 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 20:357–362

    Article  CAS  PubMed  Google Scholar 

  • 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 9:2817–2825

    Google Scholar 

  • 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 23:1347–1355

    CAS  PubMed  Google Scholar 

  • Raich PC, Lu J, Thompson HJ, Combs GF Jr (2001) Selenium in cancer prevention: clinical issues and implications. Cancer Invest 19:540–553

    Article  CAS  PubMed  Google Scholar 

  • 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 64:2143–2147

    CAS  PubMed  Google Scholar 

  • Ravi R, Bedi A (2004) NF-kappa B in cancer-a friend turned foe. Drug Resist Update 7:53–67

    Article  CAS  Google Scholar 

  • Rayman MP, Rayman MP (2002) The argument for increasing selenium intake. Proc Nutr Soc 61:203–215

    Article  CAS  PubMed  Google Scholar 

  • Rees BJ, Ye JL (1999) Pyrrhoglossum and the small-spored species of Gymnopilus (Cortinariaceae) in eastern Australia. Aust Syst Bot 12:255–270

    Google Scholar 

  • Ross GD, Vetvicka V, Yan J, Xia Y, Vetvickova J (1999) Therapeutic intervention with complement and beta-glucan in cancer. Immunopharmacology 42:61–74

    Google Scholar 

  • Safir N, Wendel A, Saile R, Chabraoui L (2003) The effect of selenium on immune functions of J774.1 cells. Clin Chem Lab Med 41:1005–1011

    Google Scholar 

  • 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 13:671–675

    CAS  PubMed  Google Scholar 

  • 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 155:650–655

    CAS  PubMed  Google Scholar 

  • Scappaticci FA (2002) Mechanisms and future directions for angiogenesis-based cancer therapies. J Clin Oncol 20:3906–3927

    Article  CAS  PubMed  Google Scholar 

  • 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 22:343–349

    Article  CAS  PubMed  Google Scholar 

  • Shah DT, Larsen B (1991) Clinical isolates of yeast produce a gliotoxin-like substance. Mycopathologia 116:203–208

    CAS  PubMed  Google Scholar 

  • 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 45:387–392

    Article  PubMed  Google Scholar 

  • 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 53:1137–1144

    CAS  PubMed  Google Scholar 

  • Silberborth S, Stumpf A, Erkel G, Anke T, Sterner O (2002) Gerronemins A-F, cytotoxic biscatechols from a Gerronema species. Phytochemistry 59:643–648

    Article  CAS  PubMed  Google Scholar 

  • Sinha R, El-Bayoumy K (2004) Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy by selenium compounds. Curr Cancer Drug Targets 4:13–28

    CAS  PubMed  Google Scholar 

  • 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 75:139–155

    Article  CAS  PubMed  Google Scholar 

  • Sliva D (2003) Ganoderma lucidum (reishi) in cancer treatment. Integr Cancer Ther 2:358–364

    Google Scholar 

  • 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 298:603–612

    Article  CAS  PubMed  Google Scholar 

  • 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 9:491–497

    Article  PubMed  Google Scholar 

  • 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 88:113–116

    Article  PubMed  Google Scholar 

  • Soussi T (2000) The p53 tumor suppressor gene: from molecular biology to clinical investigation. Ann NY Acad Sci 910:121–139

    CAS  PubMed  Google Scholar 

  • 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 138:145–150

    Article  CAS  PubMed  Google Scholar 

  • 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 4:62–66

    Google Scholar 

  • 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 12:366–380

    CAS  Google Scholar 

  • Takaku T, Kimura Y, Okuda H (2001) Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action. J Nutr 131:1409–1413

    CAS  PubMed  Google Scholar 

  • Taketo MM (1998a) Cyclooxygenase-2 inhibitors in tumorigenesis (part I). J Natl Cancer Inst 90:1529–1536

    Google Scholar 

  • Taketo MM (1998b) Cyclooxygenase-2 inhibitors in tumorigenesis (part II). J Natl Cancer Inst 90:1609–1620

    Google Scholar 

  • 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 61:193–197

    Google Scholar 

  • Topcu Z (2001) DNA topoisomerases as targets for anticancer drugs. J Clin Pharm Ther 26:405–416

    Article  CAS  PubMed  Google Scholar 

  • Tzianabos AO (2000) Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev 13:523–533

    Article  CAS  PubMed  Google Scholar 

  • 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 24:59–65

    PubMed  Google Scholar 

  • Venkateswaran V, Klotz LH, Fleshner NE (2002) Selenium modulation of cell proliferation and cell cycle biomarkers in human prostate carcinoma cell lines. Cancer Res 62:2540–2545

    CAS  PubMed  Google Scholar 

  • 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 159:599–605

    Google Scholar 

  • 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 21:21–30

    Article  CAS  PubMed  Google Scholar 

  • Wada T, Penninger JM (2004) Mitogen-activated protein kinases in apoptosis regulation. Oncogene 23:2838–2849

    Article  CAS  PubMed  Google Scholar 

  • 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 22:559–564

    PubMed  Google Scholar 

  • Waring P, Eichner RD, Tiwari-Palni U, Mullbacher A (1987) Gliotoxin-E: a new biologically active epipolythidioxopiperazine isolated from Penicillium terlikowskii. Aust J Chem 40:991–997

    CAS  Google Scholar 

  • Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60:258–274

    Google Scholar 

  • Wasser SP, Weis AL (1999) Medicinal properties of substances occurring in higher basidiomycetes mushrooms: current perspectives (review). Int J Med Mushrooms 1:31–62

    CAS  Google Scholar 

  • 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 157:19–27

    Article  CAS  PubMed  Google Scholar 

  • 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 4:88–94

    Google Scholar 

  • 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 162:2281–2290

    Google Scholar 

  • Yamamoto Y, Gaynor RB (2004) I kappa B kinases: key regulators of the NF-kappa B pathway. Trends Biochem Sci 29:72–79

    Article  CAS  PubMed  Google Scholar 

  • 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 163:3045–3052

    Google Scholar 

  • 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 5–15

    Google Scholar 

  • 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 310–313

    Google Scholar 

  • 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 25:657–665

    Google Scholar 

  • 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 59:4413–4418

    CAS  PubMed  Google Scholar 

  • 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 50:7581–7585

    Article  CAS  PubMed  Google Scholar 

  • 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 61:7071–7078

    CAS  PubMed  Google Scholar 

  • 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 6:287-314

    Google Scholar 

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Acknowledgements We thank Prof. N. Ohno (Japan) for critical reading of the manuscript, and R. Permut for English editing. This research was supported by the Ministry of Science and Technology of Israel, grant No. 3-0561.

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  1. Biodiversity and Biotechnology Center of Cryptogamic Plants and Fungi, The Institute of Evolution, University of Haifa, Mount Carmel, Haifa, 31905, Israel

    Ben-Zion Zaidman, Majed Yassin & Solomon P. Wasser

  2. Migal–Galilee Technology Center, South Industrial Zone, P.O. Box 831, Kiryat Shmona, 11061, Israel

    Ben-Zion Zaidman, Majed Yassin & Jamal Mahajna

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  1. Ben-Zion Zaidman
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  2. Majed Yassin
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  3. Jamal Mahajna
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Correspondence to Jamal Mahajna.

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Zaidman, BZ., Yassin, M., Mahajna, J. et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl Microbiol Biotechnol 67, 453–468 (2005). https://doi.org/10.1007/s00253-004-1787-z

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