Inhibition of prostate specific antigen expression by genistein in prostate cancer cells

Recent studies have provided convincing evidence for the role of soy-isofla vones, particularly genistein, in the inhibition of prostate cancer cell gr owth. Prostate specific antigen (PSA) is a biological marker used to detect and monitor the treatment of prostate cancer patients. Previous studies ha ve documented that isoflavones can inhibit the secretion of PSA in the andr ogen-dependent prostate cancer cell line, LNCaP, however, the effects of ge nistein on androgen-independent PSA expression has not been explored. In th is study, we have utilized a prostate cancer cell line, VeCaP, which expres ses PSA in an androgen-independent manner, to determine the effects of geni stein on cell proliferation and PSA expression. Here we show that genistein inhibits cell growth similarly in both the LNCaP and VeCaP cell lines, but has differential effects on PSA expression. We demonstrate using concentra tions of genistein that have been detected in the serum of humans consuming a soy-rich diet, that genistein decreases PSA mRNA, protein expression and secretion. Conversely, only high concentrations of genistein inhibited PSA expression in VeCaP cells. Additionally, we have demonstrated that geniste in inhibits cell proliferation independent of PSA signaling pathways, provi ding further evidence to support the role of genistein as a chemopreventive /therapeutic agent for prostate cancer irrespective of androgen responsiven ess.