Abstract 5445: A novel mechanism of inhibition of ovarian cancer growth by Compound C, dorsomorphin

High grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy with a five-year survival rate of 15%. As a highly aggressive cancer, HGSC has elevated energy demands to ensure its survival and proliferation in its unique peritoneal environment. Compound C or Dorsomophin is of particular interest as it is the only available cell permeable molecule that works selectively and competitively to inhibit Adenosine Monophosphate Protein-activated protein kinase or AMPK, a sensitive sensor of ATP levels. It has long been established that Compound C has a role as a BMP1 inhibitor during embryogenesis and as an inhibitor of AMPK activity in different contexts. However, the mechanism by which Compound C exerts anti-tumorigenic effects remains unknown. The purpose of this study is to understand how Compound C suppresses growth of HGSC. Our preliminary studies indicate that Compound C inhibits ovarian cancer cell proliferation and survival via a novel mechanism not only through inhibition of AMPK but also through the inhibition of upstream PI3K-Akt as well as TGFβ1/ TGFβ1/2 receptors/Smad 3,4 activation. These findings elucidate a novel mechanism of inhibition of ovarian cancer by Compound C, suggesting its potential use as a novel therapeutic agent inhibiting oncogenic and metabolic pathways. Citation Format: Alia Ghoneum, Hesham M. Afify, Neveen Said. A novel mechanism of inhibition of ovarian cancer growth by Compound C, dorsomorphin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5445.