Gossypol, A Potent Small Molecule Inhibitor of Bcl-Xl as a Novel Molecular Targeted Therapy for Prostate Cancer

摘要

The major goal in the first year of the project is to investigate the in vitro anti-tumor activity of (-)-grossypol using prostate cancer cell lines. We have finished the tasks proposed in the Statement of Work for the first year. Specifically, we have investigated the in vitro anti-tumor activity of (-)-gossypol and potential synergistic effects of (-)-gossypol in combination with chemotherapeutic drugs. (-)-gossypol showed potent anti-tumor activity in human prostate cancer PC-3, LnCaP, CL-1 cells, but only limited or minimal effect on DU-145 and human normal prostate epithelial cells (PrEC) with low Bcl-xL. (-)-gossypol potently enhanced apoptosis induction by CDDP and docetaxel, currently used chemotherapeutic agents for prostate cancer. In PC-3 and CL-1 cells, (-) gossypol showed either additive or more than additive effects in combination of CDDP and docetaxel using MTT-based WST-1 assay. (-)- gossypol potently enhanced X-ray irradiation induced growth inhibition in a clonogenic assay, and apoptosis induction in Annexin V and PI staining assays. The data obtained in the first year provide us a solid foundation to move the project to in vivo testing and further mechanism studies, to develop (-)- gossypol as a novel molecular targeted therapy for the treatment of prostate cancer with Bcl-xL overexpression.