Genistein-induced upregulation of p21(WAF1), downregulation of cyclin B, and induction of apoptosis in prostate cancer cells

Increased soy consumption in Asian diets, resulting in increased serum isof lavone levels, has been associated with a decreased risk for prostate adeno carcinoma (PCa). The isoflavone genistein is believed to be the anticancer agent found in soy, and significant levels of genistein have been detected in human prostatic fluid, implicating the role of genistein in PCa preventi on. Recent studies have demonstrated genistein's ability to inhibit cell gr owth and induce apoptosis in several cell lines; however, the molecular mec hanisms of genistein's effect are not known. We have evaluated the mechanis m by which genistein may inhibit PCa cell growth. Here we report that genis tein inhibits PCa cell growth in culture in a dose-dependent manner, which is accompanied by a G(2)/M cell cycle arrest. Cell growth inhibition was ob served with concomitant downregulation of cyclin B, upregulation of the p21 (WAF1) growth-inhibitory protein, and induction of apoptosis. Collectively, these results provide experimental evidence for a novel effect of genistei n on cell cycle gene regulation, resulting in the inhibition of cell growth and ultimate demise of tumor cells.