Sgi-110 Alters Ovarian Cancer Stem Cells To Prevent Recurrent And Chemoresistant Ovarian Cancer

Ovarian cancer stem cells (OCSCs) are associated with drug resistance and tumor relapse. Epigenetic aberrations, especially DNA methylation, result in silencing of tumor suppressor and differentiation-associated genes and regulate OCSCs9 survival. To test the hypothesis that DNA hypomethylating agents can “reset” OCSCs towards differentiation, we investigated the effect of the DNA methytransferase inhibitor SGI-110 on OCSCs, defined by aldehyde dehydrogenase 1 (ALDH)(+) cells. We treated ALDH(+) cells from platinum-sensitive A2780 and platinum-resistant A2780-cp OC cells with SGI-110 (100nM, 72 hr) or with cisplatin (CDDP; 1.67M, 24hr). After a 4 day recovery period, %ALDH+ was analyzed using FACS, cell viability was determined, and ALDH(+) cells were grown as spheroids in culture or as xenografts in mice. The overall %ALDH+ cells was higher (P Citation Format: Yinu Wang, Horacio Cardenas, Fang Fang, Salvatore Condello, Pietro Taverna, Gavin Choy, Mohammad Azab, Kenneth Nephew, Daniela Matei. SGI-110 alters ovarian cancer stem cells to prevent recurrent and chemoresistant ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2317. doi:10.1158/1538-7445.AM2014-2317