Effects of Serum on (-)-Gossypol-suppressed Growth in Human Prostate Cancer Cells

Abstract

Background: Gossypol, a natural polyphenolic compound present in cottonseeds, possesses antiproliferative and pro-apoptotic effects in in vivo and in vitro models. There are two enantiomers, (+)-gossypol and (-)-gossypol, the latter being a more potent inhibitor of cancer cell growth. Here, the effect of bovine serum albumin (BSA) and dextran-coated charcoal-treated fetal bovine serum (DCC-FBS)-containing medium on the ability of (-)-gossypol to inhibit the growth of human prostate cancer cells was studied. Materials and Methods: BSA- and DCC-FBS-supplemented medium were used to examine the influence of serum proteins on the antiproliferative effects of (-)-gossypol in DU-145 cells, a human prostate cancer cell line. The viability of the DU-145 cells was determined by CellTiter 96™ Aqueous assay. The expressions of mRNA and protein for the cell cycle regulators, cyclin-D1, Rb, CDK, p21 and TGF-β, were determined by RT-PCR and Western blot analyses, respectively. Results: (-)-Gossypol caused growth suppression of the DU-145 cells. In comparison with BSA-supplemented medium, DCC-FBS blocked the antiproliferative effects of (-)-gossypol at 1 and 2.5 μM, but not at 5 μM. Furthermore, (-)-gossypol treatment down-regulated cyclin-D1, Rb, CDK4 and CDK6, and up-regulated p21 and TGF-β1 at the mRNA and/or protein levels. Conclusion: The data suggested that (-)-gossypol-suppressed prostate cancer cell growth may be influenced through cell cycle regulators, which may lead to better prognosis. We further speculate that (-)-gossypol might serve as a chemotherapeutic agent for human prostate cancer patients.