Genistein inhibits NF-kappa B activation in prostate cancer cells

Prostate cancer is the second leading cause of cancer-related deaths in men in the United States. Epidemiological studies indicate that susceptibility to prostate cancer may be partly due to environmental influences, especial ly diet. An association has been shown between decreased prostate cancer ri sk and mortality with increased consumption of soy products, resulting in i ncreased levels of isoflavones. We previously demonstrated that the soy iso flavone genistein inhibits cell growth and induces apoptosis in prostate ca ncer cells. To further elucidate the molecular mechanism by which genistein elicits its apoptotic effect, we investigated the role of a transcription factor, nuclear factor-kappa B (NF-kappa B), in the androgen-sensitive cell line LNCaP and the androgen-insensitive cell line PC3. Here we show that g enistein decreases NF-kappa B DNA binding and abrogates NF-kappa B activati on by DNA-damaging agents, H2O2 and tumor necrosis factor-alpha, in prostat e cancer cells regardless of androgen sensitivity. Additionally, we have de monstrated that genistein reduces phosphorylation of the inhibitory protein I kappa B alpha and block the nuclear translocation of NF-kappa B, prohibi ting DNA binding and preventing NF-kappa B activation. These results provid e a mechanism by which genistein induces apoptosis in prostate cancer cells . the inactivation of NF-kappa B. Furthermore, genistein's ability to abrog ate NF-kappa B activation by DNA-damaging agents strongly supports genistei n 's role as a chemopreventive agent.