Abstract 675: Effect of Progesterone on Antioxidant Activity in Cancer Cells

Abstract

Abstract Progesterone (P4) has been implicated as a protective factor for epithelial ovarian and endometrial cancers, yet little is known about its mechanism of action. We previously reported that pregnancy-equivalent doses of P4 inhibited the growth of normal and malignant human ovarian surface epithelial (HOSE) and endometrial cells. Increased generation of reactive oxygen species (ROS) and an altered redox status have been observed in cancer cells. Here, we investigated if P4-induces cell death by modulating major antioxidant enzymes. The exposure of ovarian and endometrial cancer cell cultures to 10−6 M P4 induced time-dependent increases in early and late apoptotic cells and activation of caspase-3. A general caspase inhibitor Z-VAD effectively blocked the P4- induced cell death in a dose-dependent manner. Expression levels of glutathione peroxidase (GPX1), NAD(P)H:quinine oxidoreductase (NQO1) and copper and zinc SOD (CuZnSOD) were high in cancer cells. Treatment of cancer cells with progesterone at 10−8 M for a period of 72 h induced significant loss of GPX1, NQO1 and CuZnSOD protein expression. The inhibitory action of progesterone was blocked by the specific progesterone antagonist (miferpristone, 10−5 M), confirming P4 specificity. Further investigation on the regulation of antioxidant enzymes by P4 may provide new insights into P4's anticancer activities and facilitate the development of new strategies to use P4 as an anticancer agent. 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 675.