Cytotoxic effect of gossypol on colon carcinoma cells

Gossypol, a male contraceptive drug extracted from cottonseeds, has been fo und to have antiproliferative activity on tumour cells and is thought to be a potential anticancer drug. The aim of this study was to investigate the mechanisms of gossypol-induced cell death on two colon carcinoma cell lines , HT29 and LoVo. Firstly, we studied the effect of gossypol on the colony f orming ability of these tumour cells, which is the main target of chemother apeutic drugs. Using clonogenic assays, flow cytometry and DNA gel electrop horesis techniques, we have found that gossypol not only inhibited colony f orming ability of these tumour cells, but we also observed cellular internu cleosomal DNA fragmentation in the cells treated with 3 doses of gossypol a nd this was accompanied by the appearance of a sub-G1 apoptotic peak and mo rphological characteristics of apoptosis. Our results suggest that the goss ypol induced cell death is via an apoptotic pathway and the effect of gossy pol may not be cell cycle specific. Using Western blotting analysis, we fou nd that the gossypol-induced apoptosis may not be involved in the regulatio n of p53 but possibly associated with the regulation of bcl-2 and Bax expre ssion. Our evidence indicates that gossypol may provide a potential therape utic benefit for the treatment of colon carcinoma and understanding the mec hanisms of gossypol-induced cytotoxicity on tumour cells is essential for i ncluding this drug in clinical use. (C) 2000 Elsevier Science Inc. All righ ts reserved.