OLAPARIB AND RESVERATROL COMBINATION INDUCES ANTIPROLIFERATIVE EFFECT IN CASTRATION RESISTANT PROSTATE CANCER CELL LINE DU-145

Prostate cancer is aggressive when it becomes castration resistant. Current therapies include androgen deprivation, complete androgen blockade, immunotherapies, DNA repair mechanism and next generation hormonal drugs. Combinational therapies are also popular and promising for aggressive prostate tumors. Olaparib is an FDA approved drug that provides PARP inhibition in DNA damage response. Resveratrol is a natural compound that contributes to treatments for many diseases including cancers. In this study, the anti-proliferative effects of combination therapy of Olaparib and Resveratrol was investigated on castration resistant prostate cancer cell line DU-145. Anti-proliferative effect and growth inhibition of Olaparib and Resveratrol was determined by Resazurin assay and clonogenic assay, respectively. Cell cycle assay was used to determine the cell distribution. Cell death and Reactive Oxygen Species (ROS) production was determined by apoptosis and ROS assay, respectively. We observed significant decreases in the DU-145 cell population in cell viability and cell growth assays. We also examined the effects of this combination on the cell cycle and found that the combination group increased DNA content in the G2/M phase. There was no significant effect on ROS production. Finally, the Annexin V/PI assay showed cell death in combination group of DU-145 cells. Combination treatment of Olaparib and Resveratrol showed anti-proliferative and anti-cancer effect on castration resistant prostate cancer DU-145 cell line.