Mitochondrial Apoptosis: A New Foundation for Combing Agents in Prostate Cancer Treatment

摘要

Mitochondrial Apoptosis: A New Foundation for Combing Agents in Prostate Cancer Treatment. Charles E. Myers, M.D. This grant sought to examine synergy between androgen withdrawal and drugs known to have activity against hormone-refractory prostate cancer. The hypothesis is that apoptosis induced by these various agents would converge on mitochondria enhancing tumor cell kill. During the first year, we were able to clearly show that none of the agents tested were synergistic or even additive with hormonal therapy. However, we did find promising synergy between HMG-Co reductase inhibitors or phenylbutyrate on one hand and the chemotherapy drugs, taxol, etoposide and suramin. Our original hypothesis of synergy between androgen withdrawal and apoptosis induced by chemotherapy was predicted on the idea that all of these agents converged on mitochondria as the common pathway to apoptosis. We sought the explanation for the failure of this hypothesis. We found that prostate cancer cells contain large amounts of preformed FAS and FAS-L that are sequestered at distinct intracellular sites. In addition to mitochondrial apoptosis, rapid translocation of FAS or FAS-L to the cell surface represent a second independent pathway to cell death.