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 anticancer activity.
Gossypolone, the major metabolite of
gossypol, also prossesses 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 proliferation of
hormone-dependent and
hormone-independent human
breast carcinoma cells, i.e., MCF-7, MCF-7 Adr and MDA-MB-231 cells.
Gossypol and
gossypolone were examined at concentrations up to 10 microM, and cellular
DNA synthesis was monitored by 3H-thymidine incorporation.
Gossypol and
gossypolone produced dose-dependent suppression of
DNA synthesis in all of the human breast cell lines examined.
Gossypol produced potent antiproliferative activity in MCF-7 cells at doses as low as 30 nM. Co-incubation of MCF-7 cells with
gossypol (5 microM) and
estradiol (10 nM) did not alter the effects of gossypl. Treatment of human
breast cancer cells with 2.5 microM of
gossypol resulted in alterations in cell shape and attachment to the surface of the culture dishes. At
gossypol doses of 10 microM, pericytoplasmic globuation and cytoplasmic swelling were observed in the majority of
breast cancer cells. These changes in cellular morphology indicate a loss of ability of the cells to maintain normal cell membrane permeability, resulting in subsequent disorganization and loss of cytoplasmic organelles.
Gossypolone is less potent than
gossypol in producing these effects in the human
breast cancer cell lines, whereas it possesses equipotent antisteroidogenic and antireproductive activities with
gossypol. These investigations suggest that
gossypol and
gossypol analogs may have therapeutic potential for human
breast cancer.