QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takaku, T. Articles by Okuda, H. Search for Related Content PubMed PubMed Citation Articles by Takaku, T. Articles by Okuda, H.

---

Articles

Isolation of an Antitumor Compound from Agaricus blazei Murill and Its Mechanism of Action¹

Takeshi Takaku^*, Yoshiyuki Kimura² and Hiromichi Okuda

Second Department of Medical Biochemistry and ^* Central Research Laboratory, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan

²To whom correspondence should be addressed. E-mail: yokim{at}m.ehime-u.ac.jp

The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer, diabetes, hyperlipidemia, arteriosclerosis and chronic hepatitis. In the present study, we examined the antitumor activities of various substances isolated from the lipid fraction of A. blazei. Tumor growth was retarded by the oral administration of the lipid fraction extracted from A. blazei with a chloroform/methanol mixture in sarcoma 180–bearing mice. The substance with the antitumor activity in the lipid fraction was isolated via silica gel column chromatography, eluted with an acetonitrile/methanol (3:2) mixture and identified as ergosterol by direct comparison of the ¹H NMR and mass spectrometry spectral data of an authentic sample. The oral administration of ergosterol to sarcoma 180–bearing mice significantly reduced tumor growth at doses of 400 and 800 mg/kg administered for 20 d without side effects, such as the decreases in body, epididymal adipose tissue, thymus, and spleen weights and leukocyte numbers induced by cancer chemotherapy drugs. Ergosterol had no cytotoxicity against tumor cells. To clarify the antitumor activity of ergosterol, we examined the effects of ergosterol on tumor-induced angiogenesis using two in vivo models. Intraperitoneal administration of ergosterol at doses of 5, 10 and 20 mg/kg for 5 consecutive d inhibited the neovascularization induced by Lewis lung carcinoma cell–packed chambers, suggesting that either ergosterol or its metabolites may be involved in the inhibition of tumor-induced neovascularization. Therefore, we further examined the inhibitory effects of ergosterol on Matrigel-induced neovascularization. Female C57BL/6 mice were subcutaneously inoculated with Matrigel containing acidic fibroblast growth factor and heparin with or without ergosterol. Ergosterol inhibited the Matrigel-induced neovascularization, suggesting that ergosterol directly inhibits Matrigel-induced neovascularization. From these results, it seems likely that the antitumor activity of ergosterol might be due to direct inhibition of angiogenesis induced by solid tumors. This is the first report of ergosterol as an antiangiogenic substance.

KEY WORDS: • Agaricus blazei • antitumor activity • antiangiogenic activity • antitumor substance • mice

This article has been cited by other articles:

				L Ziliotto, L. Barbisan, and M. Rodrigues Lack of chemoprevention of dietary Agaricus blazei against rat colonic aberrant crypt foci Human and Experimental Toxicology, June 1, 2008; 27(6): 505 - 511. [Abstract] [PDF]

				F. Firenzuoli, L. Gori, and G. Lombardo The Medicinal Mushroom Agaricus blazei Murrill: Review of Literature and Pharmaco-Toxicological Problems Evid. Based Complement. Altern. Med., March 1, 2008; 5(1): 3 - 15. [Abstract] [Full Text] [PDF]

				M. Kawamura and H. Kasai Delayed Cell Cycle Progression and Apoptosis Induced by Hemicellulase-Treated Agaricus blazei Evid. Based Complement. Altern. Med., March 1, 2007; 4(1): 83 - 94. [Abstract] [Full Text] [PDF]

				L R Ribeiro, M S Mantovani, D A Ribeiro, and D M. Salvadori Brazilian natural dietary components (annatto, propolis and mushrooms) protecting against mutation and cancer Human and Experimental Toxicology, May 1, 2006; 25(5): 267 - 272. [Abstract] [PDF]

				E. L. Cooper Role of TOLL-like Receptors in Adjuvant-Augmented Immune Therapies by T. Seya. Evid. Based Complement. Altern. Med., March 1, 2006; 3(1): 133 - 137. [Full Text] [PDF]

				H. Kasai, L. M. He, M. Kawamura, P. T. Yang, X. W. Deng, M. Munkanta, A. Yamashita, H. Terunuma, M. Hirama, I. Horiuchi, et al. IL-12 Production Induced by Agaricus blazei Fraction H (ABH) Involves Toll-like Receptor (TLR) Evid. Based Complement. Altern. Med., December 1, 2004; 1(3): 259 - 267. [Abstract] [Full Text] [PDF]

				A. T. Borchers, C. L. Keen, and M. E. Gershwin Mushrooms, Tumors, and Immunity: An Update Experimental Biology and Medicine, May 1, 2004; 229(5): 393 - 406. [Abstract] [Full Text] [PDF]

				Y. Kimura Carp Oil or Oleic Acid, but Not Linoleic Acid or Linolenic Acid, Inhibits Tumor Growth and Metastasis in Lewis Lung Carcinoma-Bearing Mice J. Nutr., July 1, 2002; 132(7): 2069 - 2075. [Abstract] [Full Text] [PDF]