ANTIPROLIFERATIVE ACTIVITY OF GOSSYPOL AND GOSSYPOLONE ON HUMAN BREAST-CANCER CELLS

Gossypol is a polyphenolic aldehyde occurring naturally in cottonseed that produces antisteroidogenic activity in vivo, has been extensively investigated as a male contraceptive agent, and has demonstrated anti cancer activity. Gossypolone, the major metabolite of gossypol, also p rossesses antisteroidogenic activity but has not been examined for its anticancer properties. The objectives of these investigations are to compare the effects of gossypolone with those of gossypol on cell prol iferation of hormone-dependent and hormone-independent human breast ca rcinoma cells, i.e., MCF-7, MCF-7(Adr) and MDA-MB-231 cells. Gossypol and gossypolone were examined at concentrations upto 10 mu M, and cell ular DNA synthesis was monitored by H-3-thymidine incorporation. Gossy pol and gossypolone produced dose-dependent suppression of DNA synthes is in all of the human breast cell lines examined. Gossypol produced p otent antiproliferative activity in MCF-7 cells at doses as low as 30 nM. Co-incubation of MCF-7 cells with gossypol (5 mu M) and estradiol (10 nM) did not alter the effects of gossypol. Treatment of human brea st cancer cells with 2.5 mu M of gossypol resulted in alterations in c ell shape and attachment to the surface of the culture dishes. At goss ypol doses of 10 mu M, pericytoplasmic globuation and cytoplasmic swel ling were observed in the majority of breast cancer cells. These chang es in cellular morphology indicate a loss of ability of the cells to m aintain normal cell membrane permeability, resulting in subsequent dis organization and loss of cytoplasmic organelles. Gossypolone is less p otent than gossypol in producing these effects in the human breast can cer cell lines, whereas it possesses equipotent antisteroidogenic and antireproductive activities with gossypol. These investigations sugges t that gossypol and gossypol analogs may have therapeutic potential fo r human breast cancer.