Abstract 610: The role of oxidative stress in the growth inhibitory and proapoptotic effects of brown button mushrooms (Agaricus bisporus) in human prostate cancer cells

Abstract

Abstract An increasing body of clinical and in vivo/in vitro studies suggests that some chemical components in specialty mushrooms like maitake (Grifola frondosa) may exert cancer preventive effects. Edible mushrooms, which have a similar content of polysaccharides, proteoglycans, steroids, etc., have been less well-studied for their anticancer and cancer preventive activity. For example, only one publication has reported the inhibition of human breast cancer cell growth by brown button mushrooms (Agaricus bisporus). The objectives of our research were to evaluate the anti-prostate cancer activity and mechanism(s) of action of brown button mushroom extracts. A hot water extract was prepared from freeze-dried brown button mushroom powder and fractioned with hexane and ethyl acetate. The IC50 of ethyl acetate fraction from brown button mushrooms (BBEA) was ∼0.1mg/ml. The inhibitory potency against LNCaP human prostate cancer cells correlated with the total phenol content, suggesting that these may be the active anticancer components. To further investigate the mechanisms of BBEA's anticancer effects, we examined the production of H2O2 by the extract using FOX assay and examined oxidative stress, proapoptotic, and cell cycle arrest markers by western blot. BBEA (0.1mg/ml) produced ∼50µM H2O2 under cell culture conditions after 6h. The expression of the oxidative stress marker, αH2A.X, in LNCaP cells was enhanced by BBEA after 12 and 24h, suggesting that pro-oxidative effects may be a possible anticancer mechanism. BBEA also increased caspase-3 and PARP cleavage and reduced the expression of Cyclin D1 and Cyclin E2, suggesting induction of apoptosis and cell cycle arrest by BBEA. In summary, this is the first report of the anticancer effects of phenolic compounds in brown button mushrooms and these results demonstrate that further study of BBEA is warranted. Microarray studies are currently under way to better characterize the anticancer activity of BBEA against human prostate cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 610. doi:1538-7445.AM2012-610