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Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells

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Abstract

In this study, we screened a total of 201 diethyl ether, ethanol, and ethyl acetate fungal Basidiomycetes extracts for anti-androgenic activity. Based on our screened results in combination with the selective inhibition of prostate cancer LNCaP cells, we selected Coprinus comatus and Ganoderma lucidum for further evaluation. We demonstrated that ethanol and ethyl acetate extracts from C. comatus and G. lucidum, respectively, selectively inhibit dihydrotestosterone-induced LNCaP cell viability, suppress levels of secreted prostate-specific antigen in a dose-dependent manner, and cause a G1 phase arrest in LNCaP, but not in DU 145 and PC-3 cells. For the first time, to the best of our knowledge, we demonstrated that C. comatus and G. lucidum decreased androgen and glucocorticoide receptors transcriptional activity in breast cancer MDA-kb2 cells in a dose-dependent manner, and suppressed androgen receptor (AR) protein level in LNCaP and MDA-kb2 cells. Our findings suggest that AR and non-AR mediated mechanisms underlie the effects of C. comatus and G. lucidum.

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References

  1. Bindukumar B, Schwartz SA, Nair MP, Aalinkeel R, Kawinski E, Chadha KC (2005) Prostate-specific antigen modulates the expression of genes involved in prostate tumor growth. Neoplasia 7(3):241–252

    Article  PubMed  CAS  Google Scholar 

  2. Burnstein KL (2005) Regulation of androgen receptor levels: implications for prostate cancer progression and therapy. J Cell Biochem 95(4):657–669

    Article  PubMed  CAS  Google Scholar 

  3. Chan CC, Lao TT, Ho PC, Sung EO, Cheung AN (2003) The effect of mifepristone on the expression of steroid hormone receptors in human decidua and placenta: a randomized placebo-controlled double-blind study. J Clin Endocrinol Metab 88(12):5846–5850

    Article  PubMed  CAS  Google Scholar 

  4. Cifuentes E, Croxen R, Menon M, Barrack ER, Reddy GP (2003) Synchronized prostate cancer cells for studying androgen regulated events in cell cycle progression from G1 into S phase. J Cell Physiol 195(3):337–345

    Article  PubMed  CAS  Google Scholar 

  5. DePrimo SE, Diehn M, Nelson JB, Reiter RE, Matese J, Fero M, Tibshirani R, Brown PO, Brooks JD (2002) Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biol 3(7):RESEARCH0032

    Article  PubMed  Google Scholar 

  6. Fenton MA, Shuster TD, Fertig AM, Taplin ME, Kolvenbag G, Bubley GJ, Balk SP (1997) Functional characterization of mutant androgen receptors from androgen-independent prostate cancer. Clin Cancer Res 3(8):1383–1388

    PubMed  CAS  Google Scholar 

  7. Fujita R, Liu J, Shimizu K, Konishi F, Noda K, Kumamoto S, Ueda C, Tajiri H, Kaneko S, Suimi Y, Kondo R (2005) Anti-androgenic activities of Ganoderma lucidum. J Ethnopharmacol 102(1):107–112

    Article  PubMed  Google Scholar 

  8. Gao JJ, Min BS, Ahn EM, Nakamura N, Lee HK, Hattori M (2002) New triterpene aldehydes, lucialdehydes A-C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull (Tokyo) 50(6):837–840

    Article  CAS  Google Scholar 

  9. Gelmann EP (2002) Molecular biology of the androgen receptor. J Clin Oncol 20(13):3001–3015

    Article  PubMed  CAS  Google Scholar 

  10. Gonzalez del Val A, Platas G, Arenal F, Orihuela JC, Garcia M, Hernandez P, Royo I, De Pedro N, Silver LL, Young K, Vicente MF, Pelaez F (2003) Novel illudins from Coprinopsis episcopalis (syn. Coprinus episcopalis), and the distribution of illudin-like compounds among filamentous fungi. Mycol Res 107(Pt 10):1201–1209

    Article  CAS  Google Scholar 

  11. Gregory CW, Johnson RT Jr, Mohler JL, French FS, Wilson EM (2001) Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res 61(7):2892–2898

    PubMed  CAS  Google Scholar 

  12. Hartig PC, Bobseine KL, Britt BH, Cardon MC, Lambright CR, Wilson VS, Gray LE Jr (2002) Development of two androgen receptor assays using adenoviral transduction of MMTV-luc reporter and/or hAR for endocrine screening. Toxicol Sci 66(1):82–90

    Article  PubMed  CAS  Google Scholar 

  13. 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(3):250–253

    Article  PubMed  CAS  Google Scholar 

  14. Jiang J, Slivova V, Harvey K, Valachovicova T, Sliva D (2004) Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling. Nutr Cancer 49(2):209–216

    Article  PubMed  CAS  Google Scholar 

  15. Jiang J, Slivova V, Valachovicova T, Harvey K, Sliva D (2004) Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3. Int J Oncol 24(5):1093–1099

    PubMed  CAS  Google Scholar 

  16. Kojima H, Katsura E, Takeuchi S, Niiyama K, Kobayashi K (2004) Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells. Environ Health Perspect 112(5):524–531

    Article  PubMed  CAS  Google Scholar 

  17. Kuil CW, Berrevoets CA, Mulder E (1995) Ligand-induced conformational alterations of the androgen receptor analyzed by limited trypsinization. Studies on the mechanism of antiandrogen action. J Biol Chem 270(46):27569–27576

    Article  PubMed  CAS  Google Scholar 

  18. Lee C, Sutkowski DM, Sensibar JA, Zelner D, Kim I, Amsel I, Shaw N, Prins GS, Kozlowski JM (1995) Regulation of proliferation and production of prostate-specific antigen in androgen-sensitive prostatic cancer cells, LNCaP, by dihydrotestosterone. Endocrinology 136(2):796–803

    Article  PubMed  CAS  Google Scholar 

  19. 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(21):2381–2390

    Article  PubMed  CAS  Google Scholar 

  20. Long RM, Morrissey C, Fitzpatrick JM, Watson RW (2005) Prostate epithelial cell differentiation and its relevance to the understanding of prostate cancer therapies. Clin Sci 108(1):1–11

    Article  PubMed  CAS  Google Scholar 

  21. Lu QY, Jin YS, Zhang Q, Zhang Z, Heber D, Go VL, Li FP, Rao JY (2004) Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro. Cancer Lett 216(1):9–20

    Article  PubMed  CAS  Google Scholar 

  22. Montgomery BT, Young CY, Bilhartz DL, Andrews PE, Prescott JL, Thompson NF, Tindall DJ (1992) Hormonal regulation of prostate-specific antigen (PSA) glycoprotein in the human prostatic adenocarcinoma cell line, LNCaP. Prostate 21(1):63–73

    Article  PubMed  CAS  Google Scholar 

  23. Niu YJ, Ma TX, Zhang J, Xu Y, Han RF, Sun G (2003) Androgen and prostatic stroma. Asian J Androl 5(1):19–26

    PubMed  CAS  Google Scholar 

  24. Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, Raisin CJ, Dunn-Emke S, Crutchfield L, Jacobs FN, Barnard RJ, Aronson WJ, McCormac P, McKnight DJ, Fein JD, Dnistrian AM, Weinstein J, Ngo TH, Mendell NR, Carroll PR (2005) Intensive lifestyle changes may affect the progression of prostate cancer. J Urol 174(3):1065–1069; discussion 1069–1070

    Google Scholar 

  25. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108

    Article  PubMed  Google Scholar 

  26. Reina M, Orihuela JC, Gonzalez-Coloma A, de Ines C, de la Cruz M, Gonzalez del Val A, Torno JR, Fraga BM (2004) Four illudane sesquiterpenes from Coprinopsis episcopalis. Phytochemistry 65(4):381–385

    Article  PubMed  CAS  Google Scholar 

  27. Rosenhagen MC, Soti C, Schmidt U, Wochnik GM, Hartl FU, Holsboer F, Young JC, Rein T (2003) The heat shock protein 90-targeting drug cisplatin selectively inhibits steroid receptor activation. Mol Endocrinol 17(10):1991–2001

    Article  PubMed  CAS  Google Scholar 

  28. Singh SM, Gauthier S, Labrie F (2000) Androgen receptor antagonists (antiandrogens): structure–activity relationships. Curr Med Chem 7(2):211–247

    PubMed  CAS  Google Scholar 

  29. Sliva D (2004) Cellular and physiological effects of Ganoderma lucidum (Reishi). Mini Rev Med Chem 4(8):873–879

    PubMed  CAS  Google Scholar 

  30. Small EJ, Roach M 3rd (2002) Prostate-specific antigen in prostate cancer: a case study in the development of a tumor marker to monitor recurrence and assess response. Semin Oncol 29(3):264–273

    Article  PubMed  CAS  Google Scholar 

  31. Smith J, Rowan N, Sullivan R (2002) Medicinal mushrooms: their therapeutic properties and current medical usage with special emphasis on cancer treatments. University of Strathclyde, Glasgow

    Google Scholar 

  32. Stanley G, Harvey K, Slivova V, Jiang J, Sliva D (2005) Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-beta1 from prostate cancer cells. Biochem Biophys Res Commun 330(1):46–52

    Article  PubMed  CAS  Google Scholar 

  33. Tamura H, Yoshikawa H, Gaido KW, Ross SM, DeLisle RK, Welsh WJ, Richard AM (2003) Interaction of organophosphate pesticides and related compounds with the androgen receptor. Environ Health Perspect 111(4):545–552

    Article  PubMed  CAS  Google Scholar 

  34. Turner KJ, McIntyre BS, Phillips SL, Barlow NJ, Bowman CJ, Foster PM (2003) Altered gene expression during rat Wolffian duct development in response to in utero exposure to the antiandrogen linuron. Toxicol Sci 74(1):114–128

    Article  PubMed  CAS  Google Scholar 

  35. Tzianabos AO (2000) Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin Microbiol Rev 13(4):523–533

    Article  PubMed  CAS  Google Scholar 

  36. Vanaja DK, Mitchell SH, Toft DO, Young CY (2002) Effect of geldanamycin on androgen receptor function and stability. Cell Stress Chaperones 7(1):55–64

    Article  PubMed  CAS  Google Scholar 

  37. Wang LG, Liu XM, Kreis W, Budman DR (1998) Androgen antagonistic effect of estramustine phosphate (EMP) metabolites on wild-type and mutated androgen receptor. Biochem Pharmacol 55(9):1427–1433

    Article  PubMed  CAS  Google Scholar 

  38. Wilson VS, Bobseine K, Lambright CR, Gray LE Jr (2002) A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists. Toxicol Sci 66(1):69–81

    Article  PubMed  CAS  Google Scholar 

  39. Wolk A (2005) Diet, lifestyle and risk of prostate cancer. Acta Oncologica 44(3):277–281

    Article  PubMed  Google Scholar 

  40. Wong C, Kelce WR, Sar M, Wilson EM (1995) Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide. J Biol Chem 270(34):19998–20003

    Article  PubMed  CAS  Google Scholar 

  41. Wu TS, Shi LS, Kuo SC (2001) Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod 64: 1121–1122

    Article  PubMed  CAS  Google Scholar 

  42. Yang HL (2005) Ganoderic acid produced from submerged culture of Ganoderma lucidum induces cell cycle arrest and cytotoxicity in human hepatoma cell line BEL7402. Biotechnol Lett 27(12):835–838

    Article  PubMed  CAS  Google Scholar 

  43. Yang Q, Fung KM, Day WV, Kropp BP, Lin HK (2005) Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival. Cancer Cell Int 5(1):8

    Article  PubMed  CAS  Google Scholar 

  44. Zaidman BZ, Yassin M, Mahajna J, Wasser SP (2005) Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl Microbiol Biotechnol 67(4):453–468

    Article  PubMed  CAS  Google Scholar 

  45. Zhu HS, Yang XL, Wang LB, Zhao DX, Chen L (2000) Effects of extracts from sporoderm-broken spores of Ganoderma lucidum on HeLa cells. Cell Biol Toxicol 16(3):201–206

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank R. Permut (Israel) for the English editing. This research was supported by the Ministry of Science and Technology of Israel, grant no. 3-0561.

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Authors and Affiliations

  1. Institute of Evolution, University of Haifa, Mount Carmel, Haifa, 31905, Israel

    Ben-Zion Zaidman, Solomon P. Wasser & Eviatar Nevo

  2. Cancer Drug Discovery Program, Migal, Galilee Technology Center, P.O. Box 831, Kiryat Shmona, 11016, Israel

    Ben-Zion Zaidman & Jamal Mahajna

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  1. Ben-Zion Zaidman
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  2. Solomon P. Wasser
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Correspondence to Jamal Mahajna.

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Zaidman, BZ., Wasser, S.P., Nevo, E. et al. Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function in LNCaP prostate cancer cells. Mol Biol Rep 35, 107–117 (2008). https://doi.org/10.1007/s11033-007-9059-5

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  • DOI: https://doi.org/10.1007/s11033-007-9059-5

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