Abstract 5043: Molecular mechanism of resveratrol induced cell death in multidrug resistance prostate cancer

Abstract

Abstract In order to understanding the molecular mechanisms of drug resistance as well as enhancing the efficacy of docetaxel we established docetaxel-resistant prostate cancer (PCa) cells. The IC50 for docetaxel in PCa resistant cells was about 50-fold higher than parental PCa cells. In the current study we used resveratrol (RES), a natural compound with chemo preventive potential to test its ability to enhance the effectiveness of docetaxel on PCa as well as to explore the mechanism of acquired docetaxel resistance. PCa (PC3, C4-2B and DU145) cell lines treated with different dose of RES or DTX alone or in combination followed by analyzed cell proliferation (MTT assay), apoptosis (flow-cytometric analysis of annexin V/propidium iodide-stained cells and western blot methods).The expression of ABC transporter markers in the development of docetaxel resistance was examined using RT-PCR. Our result shows that the expression of 18 ABC transporter genes were down regulated in PCa cells at 48 and 72 hrs in RES treatment group. The up regulations of pro-apoptotic proteins (Bax, Bad, Bim) and down regulation of anti-apoptotic protein (Bcl2, Mcl1) further confirmed the effectiveness of RES or DTX alone or in combination with DTX. In conclusion these studies suggest that RES inhibits ABC gene expression and resensitizes docetaxel resistant PCa cells to DTX treatment with enhancing apoptotic cell death. Citation Format: Santosh K. Singh, Saswati Banerjee, James W. Lillard, Rajesh Singh. Molecular mechanism of resveratrol induced cell death in multidrug resistance prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5043.