INHIBITION OF HUMAN PROSTATE-CANCER CELLS GROWTH BY GOSSYPOL IS ASSOCIATED WITH STIMULATION OF TRANSFORMING GROWTH-FACTOR-BETA

Gossypol (GP), an antifertility agent in males, is also capable of inh ibiting 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 CP acts as a potent inhibitor of PC3 cells as determined by thymidine incorporation assay and flow cytometric analys is. Flow cytometry revealed that treatment of PC3 cells with GP result ed in a dose- and time-dependent accumulation of cells in the G0/G1 ph ase 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 transformin g growth factor-beta(1) (TGF-beta(1)) gene expression in PC3 cells. In terestingly, the stimulatory effect of GP on TCF-beta(1) gene expressi on correlates well with its inhibitory effect on PC3 cell DNA synthesi s and its ability to arrest cells in G0/G1 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 G0/G1 phase and that this inhibitory effect may be mediated by TGF-beta 1.