(-)-Gossypol, A Potent Small Molecule Inhibitor of Bcl-Xl as a Novel Molecular Targeted Therapy for Prostate Cancer
Annual rept. 16 Jan 2004-15 Jan 2005
MICHIGAN UNIV ANN ARBOR SCHOOL OF MEDICINE
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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.
- Anatomy and Physiology
- Medicine and Medical Research