Abstract 4387: Reactive oxygen species-mediated cell death by psoralidin in prostate cancer cells

Abstract

Abstract Modulating reactive oxygen species (ROS) levels may lead to either cell proliferation or death based on the cell type. It is well established that in cancer cells the basal levels of ROS is significantly higher when compared to their normal counterparts. Thus, identifying non-toxic small molecules which induces ROS specifically in cancer cells may be of enormous importance in cancer therapy. We have previously shown that psoralidin, a natural compound derived from Psoralea corylifolia specifically induces apoptosis in prostate cancer (PCa) cells (PC-3, DU-145, LNCaP and C4-2B). In this study we dissected the role of ROS in psoralidin-induced cell death in PCa. Our results suggested that psoralidin significantly induces ROS generation in both androgen-responsive (LNCaP) and -refractory (PC-3, DU-145 and C4-2B) PCa cells when compared to normal prostate epithelial cells (PzHPv7); leading to loss of mitochondrial membrane potential and release of cytochrome-c, caspase activation (9 and 3) and induction of apoptosis. In addition, induction of ROS downregulates pAkt expression and kinase activity, NF-κB (p65, p50 and p55) and mTOR (pp70S6K and p4E-BP1)-mediated pro-survival signaling in PCa cells. On the other hand, inhibition of ROS generation by N-acetylcysteine (NAC) prevented psoralidin-mediated anticancer effects on PCa. Collectively, our results suggest that psoralidin-mediated ROS generation in PCa cells causes inhibition of survival/proliferation and induction of apoptosis. Further investigation of the mechanism of action of psoralidin may facilitate initiation of clinical trials using psoralidin for the treatment of PCa. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4387.