Skip to main content
Journal of Wood Science

Official Journal of the Japan Wood Research Society

Download PDF

Estrogen-like activity of ethanol extract of Ganoderma lucidum

Journal of Wood Science volume 55, pages 53–59 (2009)Cite this article

Abstract

The ethanol extract from the fruiting body of Ganoderma lucidum was tested for its estrogen-like activity by using the cell proliferation assay (MCF-7 cells, human breast cancer cells), as well as the estrogen receptor binding assay, and pS2 mRNA expression assay in MCF-7 cells in vitro and uterotrophic assay in vivo. The ethanol extract of G. lucidum showed signifi cant positive effects on the proliferation of MCF-7 cells. This proliferation effect is related to the estrogenic activity of G. lucidum, because this proliferation activity was inhibited by the addition of the antiestrogenic compound ICI 182,780. The ability to bind to human estrogen receptors (hERs) α and β of the ethanol extract of G. lucidum was confi rmed by using the coactivator-bacterial alkaline phosphatase system. ER-dependent cell responsibilities were investigated by examining the regulation of gene transcription for pS2 in MCF-7 cells. Our results demonstrated that the pS2 mRNA levels are significantly increased by the ethanol extract of G. lucidum via an estrogen-like manner. Additionally, young rats that received the ethanol extract of G. lucidum (200 mg/kg per day) for 3 days showed a signifi cant increase (growth approximately twofold compared with the control group) in uterine weight after each treatment, which supports the estrogen-like activity of the ethanol extract of G. lucidum in vivo. It was concluded that the ethanol extract of G. lucidum showed estrogen-like activity, which may be useful in regulating hormone levels to treat related diseases such as osteoporosis if safety is fully guaranteed.

References

  1. Persson I, Weiderpass E, Bergkvist L, Bergstrom R, Schairer C (1999) Risks of breast and endometrial cancer after estrogen and estrogen-progestin replacement. Cancer Causes Control 10:253–260

    Article  CAS  PubMed  Google Scholar 

  2. Sudhir K, Komesaroff PA (1999) Clinical review 110: cardiovascular actions of estrogens in men. J Clin Endocrinol Metab 84: 3411–3415

    Article  CAS  PubMed  Google Scholar 

  3. Cassidy A (1999) Potential tissue selectivity of dietary phytoestrogens and estrogens. Curr Opin Lipidol 10:47–52

    Article  CAS  PubMed  Google Scholar 

  4. Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA, Carlquist M (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389:753–758

    Article  CAS  PubMed  Google Scholar 

  5. Chan RY, Chen WF, Dong A, Guo D, Wong MS (2002) Estrogenlike activity of ginsenoside Rg1 derived from Panax notoginseng. J Clin Endocrinol Metab 87:3691–3695

    Article  CAS  PubMed  Google Scholar 

  6. Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19:65–96

    CAS  PubMed  Google Scholar 

  7. Shiao MS (2003) Natural products of the medicinal fungus Ganoderma lucidum: occurrence, biological activities, and pharmacological functions. Chem Rec 3:172–180

    Article  CAS  PubMed  Google Scholar 

  8. Lieu CW, Lee SS, Wang SY (1992) The effect of Ganoderma lucidum on induction of differentiation in leukemic U937 cells. Anticancer Res 12:1211–1215

    CAS  PubMed  Google Scholar 

  9. Kanayama T, Mamiya S, Nishihara T, Nishikawa J (2003) Basis of a high-throughput method for nuclear receptor ligands. J Biochem 133:791–797

    Article  CAS  PubMed  Google Scholar 

  10. Odum J, Lefevre PA, Tittensor S, Paton D, Routledge EJ, Beresford NA, Sumpter JP, Ashby J (1997) The rodent uterotrophic assay: critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay. Regul Toxicol Pharmacol 25:175–188

    Article  Google Scholar 

  11. Leclercq G, Heuson JC (1979) Physiological and pharmacological effects of estrogens in breast cancer. Biochem Biophys Acta 560:427–455

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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 102:250–253

    Article  CAS  PubMed  Google Scholar 

  14. Hsu HY, Hua KF, Lin CC, Lin CH, Hsu J, Wong CH (2004) Extract of Reishi polysaccharides induces cytokine expression via TLR4-modulated protein kinase signaling pathways. J Immunol 173:5989–5999

    Article  CAS  PubMed  Google Scholar 

  15. Soule HD, Vazguez J, Long A, Albert S, Brennan M (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J Nat Cancer Inst 51:1409–1416

    Article  CAS  PubMed  Google Scholar 

  16. Liu J, Fujita R, Shimizu K, Konishi F, Noda K, Kumamoto S, Kaneko S, Suimi Y, Kondo R (2005) The effect of strain, growth stage and cultivating condition of Ganoderma lucidum on 5α-reductase inhibition. J Wood Sci 51:189–192

    Article  CAS  Google Scholar 

  17. Tham DM, Gardner CD, Haskell WL (1998) Potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 83:2223–2235

    CAS  PubMed  Google Scholar 

  18. Brooks SC, Locke ER, Soule HD (1973) Estrogen receptor in a human cell line (MCF-7) from breast carcinoma. J Biol Chem 248:6251–6253

    CAS  PubMed  Google Scholar 

  19. Katzenellenbogen BS, Rendra KL, Norman MJ, Berthois Y (1987) Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the shortterm and long-term absence. Cancer Res 47:4355–4360

    CAS  PubMed  Google Scholar 

  20. Berthois Y, Pourreau-Schneider N, Gandilhon P, Mittre H, Tubiana N, Martin PM (1986) Estradiol membrane binding sites on human breast cancer cell lines. J Steroid Biochem 25:963–972

    Article  CAS  PubMed  Google Scholar 

  21. Constantinou A, Huberman E (1995) Genistein as an inducer of tumor cell differentiation: possible mechanisms of action. Proc Soc Exp Biol Med 208:109–115

    Article  CAS  PubMed  Google Scholar 

  22. Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M, Fukami Y (1987) Genistein, a specifi c inhibitor of tyrosine-specifi c protein kinases. J Biol Chem 262:5592–5595

    CAS  PubMed  Google Scholar 

  23. Guvakova MA, Surmacz E (1997) Tamoxifen interferes with the insulin-like growth factor I receptor (IGF-IR) signaling pathway in breast cancer cells. Cancer Res 57:2606–2610

    CAS  PubMed  Google Scholar 

  24. Zava DT, Duwe G (1997) Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr Cancer 27:31–40

    Article  CAS  PubMed  Google Scholar 

  25. Miodini P, Fioravanti L, Di Fronzo G, Cappelletti V (1999) The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. Br J Cancer 80:1150–1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Fioravanti L, Cappelletti V, Miodini P, Ronchi E, Brivio M, Di Fronzo G (1998) Genistein in the control of breast cancer cell growth: insights into the mechanism of action in vitro. Cancer Lett 130:143–152

    Article  CAS  PubMed  Google Scholar 

  27. Bouker KB, Hilakivi-Clarke L (2000) Genistein: does it prevent or promote breast cancer? Environ Health Perspect 108:701–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Martinez-Campos A, Amara JF, Dannies PS (1986) Antiestrogens are partial estrogen agonists for prolactin production in primary pituitary cultures. Mol Cell Endocrinol 48:127–133

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  30. Wang SY, Hsu ML, Hsu HC, Tzeng CH, Lee SS, Shiao MS, Ho CK (1997) The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes. Int J Canc 70:699–705

    Article  CAS  Google Scholar 

  31. Bao XF, Wang XS, Dong Q, Fang JN, Li XY (2002) Structural features of immunologically active polysaccharides from Ganoderma lucidum. Phytochem 59:175–181

    Article  CAS  Google Scholar 

  32. 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 

  33. Fujita R, Liu J, Shimizu K, Konishi F, Noda K, Kumamoto S, Kurashiki K, Kondo R (2005) Anti-androgenic activities of Ganoderma lucidum. J Ethnopharmacol 102:107–112

    Article  PubMed  Google Scholar 

  34. Chiu SW, Wang ZM, Leung TM, Moore D (2000) Nutritional value of Ganoderma extract and assessment of its genotoxicity and antigenotoxicity using comet assays of mouse lymphocytes. Food Chem Toxicol 38:173–178

    Article  CAS  PubMed  Google Scholar 

  35. Lin ZB, Zhang HN (2004) Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol Sin 25:1387–1395

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Kuniyoshi Shimizu, Ichiko Miyamoto, Jie Liu & Ryuichiro Kondo

  2. Chlorella Industry Co. Ltd., Fukuoka, 833-0056, Japan

    Fumiko Konishi & Shoichiro Kumamoto

Authors
  1. Kuniyoshi Shimizu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ichiko Miyamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fumiko Konishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shoichiro Kumamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ryuichiro Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryuichiro Kondo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shimizu, K., Miyamoto, I., Liu, J. et al. Estrogen-like activity of ethanol extract of Ganoderma lucidum . J Wood Sci 55, 53–59 (2009). https://doi.org/10.1007/s10086-008-0992-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10086-008-0992-2

Key words

  • Ganoderma lucidum
  • Estrogenic activity
  • Menopausal syndrome