Abstract 2572: Compound C inhibits metabolic programming of ovarian cancer

Abstract

Abstract High grade serous ovarian carcinoma (HGSC) exhibits elevated energy demands to sustain rapid proliferation, survival and invasiveness. We have shown that Compound C, also known as Dorsomorphin, inhibits ovarian cancer growth, invasiveness and survival as well as interactions with mesothelial cells and macrophages. However, the effect of Compound C on metabolic programming has not been reported. The purpose of this study is to determine whether Compound C inhibits the malignant phenotypes of ovarian cancer through suppression of energy production. Therefore, we performed comprehensive metabolic profiling of ovarian cancer cells treated with Compound C. Our findings indicate that Compound C significantly inhibits ATP production in the ovarian cancer cell lines: OVCAR3, SKOV3 and IGROV1. Compound C inhibited basal and maximal mitochondrial respiration as well as the non-mitochondrial oxygen consumption in these three cell lines. Compound C had no effect on basal, induced or compensatory glycolysis. However, it significantly decreased the ratio of mitochondrial oxygen consumption rate to glycolytic proton efflux rate (mitoOCR/glycoPER), indicating a direct inhibitory effect of Compound C on mitochondrial electron transport chain and a bioenergetic shift from oxidative phosphorylation towards glycolysis. These results demonstrate for the first time, the direct inhibitory effect of Compound C on mitochondrial function as a novel mechanism of inhibition of the malignant phenotype of ovarian cancer cells. Citation Format: Alia Dawlat Ghoneum, Daniela Gonzalez, Neveen Said. Compound C inhibits metabolic programming of ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2572.