RRC ID 39958
著者 Takaku T, Kimura Y, Okuda H.
タイトル Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action.
ジャーナル J Nutr
Abstract 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 (1)H 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.
巻・号 131(5)
ページ 1409-13
公開日 2001-5-1
DOI 10.1093/jn/131.5.1409
PMID 11340091
MeSH Administration, Oral Agaricus / isolation & purification* Analysis of Variance Animals Carcinoma, Lewis Lung / drug therapy* Ergosterol / administration & dosage Ergosterol / immunology Ergosterol / pharmacology Female Injections, Intraperitoneal Male Mice Mice, Inbred C57BL Mice, Inbred ICR Neovascularization, Pathologic Plant Extracts / therapeutic use* Sarcoma 180 / drug therapy* Spleen / drug effects Spleen / immunology
IF 4.281
引用数 207
WOS 分野 NUTRITION & DIETETICS
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