Gossypol arrests human benign prostatic hyperplastic cell growth at G0/G1 phase of the cell cycle

Recently we demonstrated that gossypol (GP), a male antifertility agent, is a potent inhibitor of malignant human prostate cancer cell growth that acts by arresting cells in G0/G1 phase and that this inhibitory effect may be mediated by transforming growth factor-beta 1 (TGF-beta 1). In this study we examined the effect of GP on the growth of prostatic cells from human benign prostatic hyperplasia (BPH) patients in vitro. Consistent with its inhibitory effect on the growth of malignant human prostate cancer cells, GP also acts as a potent inhibitor of cultured human BPH cell growth as assessed by thymidine incorporation assay. These results were confirmed by flow cytometric analysis which revealed that treatment of human BPH cells with increasing concentrations of GP resulted in a dose-dependent accumulation of cells in the G0/G1 phase with a concomitant decrease in cells progressing to the S and G2/M phases. Since inhibition of prostate cancer cells by GP appears to be mediated by TGF-beta 1, we also investigated the effect of GP on TGF-beta 1 gene expression in BPH cells. The results show that GP treatment resulted in a marked elevation of TGF-beta 1 gene expression indicating that TGF-beta 1 might be involved at least in part in the inhibitory pathway that is initiated by GP.