UCLA

Prostate cancer is the leading cause of cancer death in western men. With limited treatment options for patients with castration-resistant prostate cancer, novel approaches are needed. We previously found a novel combination of two compounds that synergistically decreased prostate cancer cell viability at low concentrations. The goal of this project was to explore the mechanism by which the combination treatment leads to synergistic cell death. Molecular experiments were performed through Western blots, cell viability assays, and pull-down assays to examine cell proliferation, apoptosis, cellular redox status, JNK protein levels, and sumoylation. We found that the drug combination synergistically induces apoptosis mediated by increasing levels of reactive oxygen species. The combination treatment leads to enhanced JNK activity, which likely derives from increased sumoylation of JNK. We found a potential sumoylation site whose mutation results in drastic reduction of sumoylation of JNK.