Genistein-induced upregulation of p21WAF1, downregulation of cyclin B, and induction of apoptosis in prostate cancer cells.
Increased soy consumption in Asian diets, resulting in increased serum isoflavone levels, has been associated with a decreased risk for prostate adenocarcinoma (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 prevention. Recent studies have demonstrated genistein's ability to inhibit cell growth and induce apoptosis in several cell lines; however, the molecular mechanisms of genistein's effect are not known. We have evaluated the mechanism by which genistein may inhibit PCa cell growth. Here we report that genistein inhibits PCa cell growth in culture in a dose-dependent manner, which is accompanied by a G2/M cell cycle arrest. Cell growth inhibition was observed with concomitant downregulation of cyclin B, upregulation of the p21WAF1 growth-inhibitory protein, and induction of apoptosis. Collectively, these results provide experimental evidence for a novel effect of genistein on cell cycle gene regulation, resulting in the inhibition of cell growth and ultimate demise of tumor cells.
Department of Cancer Biology, Wayne State University School of Medicine, Harper Hospital, Detroit Medical Center, MI, USA.
J N
JN
Davis
B
B
Singh
M
M
Bhuiyan
F H
FH
Sarkar
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D019926:Cyclin B / Q000187:drug effects* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D016588:Anticarcinogenic Agents; C493956:CDKN1A protein, human; D019926:Cyclin B; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019833:Genistein