Inhibition of human prostate cancer cells growth by gossypol is associated with stimulation of transforming growth factor-β

Gossypol (GP), an antifertility agent in males, is also capable of inhibiting the proliferation of a wide range of cancer cells in vivo and in vitro. Thus, in this study we investigated the effect of GP on the growth of human androgen-independent prostate cancer cell line (PC3). The results showed that GP acts as a potent inhibitor of PC3 cells as determined by thymidine incorporation assay and flow cytometric analysis. Flow cytometry revealed that treatment of PC3 cells with GP resulted in a dose- and time-dependent accumulation of cells in the G0G1 phase with a concomitant decrease in cells progressing to the S and G2/M phases. These data support our thymidine incorporation results which indicated that GP is a potent inhibitor of PC3 cells. By ribonuclease protection assay, we also investigated the effect of GP on transforming growth factor-β1 (TGF-β1) gene expression in PC3 cells. Interestingly, the stimulatory effect of GP on TGF-β1 gene expression correlates well with its inhibitory effect on PC3 cell DNA synthesis and its ability to arrest cells in G0G1 phase. Based on these data, it can be concluded that GP is a potent inhibitor of prostate cancer cell growth that acts by arresting cells in G0G1 phase and that this inhibitory effect may be mediated by TGF-β1.