(-)-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 second year of the project is to investigate the in vivo anti-tumor activity and mechanism of action of (-)- gossypol in prostate cancer. We have investigated the in vivo anti-tumor activity of (-)- gossypol and potential synergistic effects of (-)-gossypol in combination with chemotherapy and radiation. (-)-gossypol potently enhanced anti-tumor efficacy of chemotherapeutic agents and radiation in nude mouse models of human prostate cancer. (-)-gossypol potently enhanced chemo-/radiation-induced apoptosis and anti-angiogenesis in tumors in vivo. Mechanism studies demonstrate that (-)- gossypol is a potent functional inhibitor of the antiapoptotic protein Bcl-xL, and Bcl-xL is one of the major molecular targets of (-)-gossypol in cell growth inhibition and apoptosis induction. Based on our exciting data obtained from this PCRP project, together with data from other collaborators, FDA approved (- )-gossypol for Phase I clinical trial which is ongoing with promising preliminary results. The Phase II clinical trial of (-)-gossypol for prostate cancer patients in combination with chemotherapy will start soon. We are in a good shape to reach the goal of this IDEA project: to develop (-)-gossypol as a novel molecular targeted therapy for the treatment of prostate cancer with Bcl- XL overexpression.