The (-)-enantiomer of gossypol inhibits proliferation of stromal cells derived from human breast adipose tissues by enhancing transforming growth factor beta(1) production

We report here that (-)-gossypol significantly inhibits the proliferation o f stromal cells derived from human breast adipose tissues (human breast adi pose stromal cells) in a dose-dependent manner. The mechanisms involved in the anti-proliferative action of (-)-gossypol on adipose stromal cells were also investigated. (-)-Gossypol stimulated transforming growth factor (TGF beta(1)) secretion after 24 h, and RNase protection assay showed that TGF beta(1) mRNA levels were increased as well. We also observed that TGF beta( 1) significantly inhibited the growth of human breast adipose stromal cells in a dose-dependent manner. When human breast adipose stromal cells were c o-incubated with 5 mu M (-)-gossypol and 50 mu g/ml of anti-TGF-beta(1),-be ta(2),-beta(3), antibody, growth inhibition caused by (-)-gossypol was comp letely abrogated. This study indicates that the anti-proliferative activity of (-)-gossypol on human breast adipose stromal cells may be mediated by c hanges in TGF beta(1) production.