Antioxidant Compounds And Their Effects On Ecm-Detached Ovarian Cancer Cells

Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynecological cancers. Approximately 70% of all EOC patients are diagnosed at advanced stages of the disease. In these patients, ovarian cancer cells shed from the primary tumor and accumulate in ascites in the peritoneal cavity. These shed cells have shown the ability to attach and form secondary tumors throughout the peritoneal cavity, making EOC more difficult to treat. A better understanding of the molecular mechanisms involved in the survival of ovarian cancer cells in ascites could lead to the development of improved chemotherapeutics aimed at eradicating this nonadhesive subset of cells and thus resulting in better survival rates of EOC patients. While non-tumorigenic epithelial cells require attachment to the extracellular matrix (ECM) for survival, ovarian cancer cells surviving in ascites gain the ability to survive in anchorage independence. Striking increases of reactive oxygen species (ROS) mediated by ECM-detachment has been shown to inhibit energy production and inhibit cell viability in non-tumorigenic mammary epithelial cells. Consequently, neutralization of ROS with antioxidant compounds enhance ATP production and promote survival in anchorage independence. Furthermore, previous publications from our laboratory suggest that antioxidant enzymes are critical for metabolic maintenance and survival of ECM-detached breast cancer cells. While these recent studies reveal a novel role for antioxidant activity in metastatic breast cancer, antioxidant activity and its effects on ECM-detached ovarian cancer cells has yet to be unveiled. Currently, we have found that neutralization of ROS through treatment with a variety of antioxidant compounds increases metabolic efficacy in ECM-detached ovarian cancer cells. More specifically, ECM-detached SKOV3 ovarian cancer cells treated with antioxidant compounds Trolox (a vitamin E analog), Vitamin C, and Epigallocatechin gallate (EGCG) results in large increases in ATP levels. Given these data, we are further working to understand the mechanisms involved in this metabolic increase. In addition, we are working to understand the relationship between this increase in metabolism and survival in anchorage independence. Future studies include looking at this phenomenon in other ovarian cancer cell lines as well as using mouse xenograft studies to examine the effects of antioxidant compounds on survival of metastatic ovarian cancer cells. Citation Format: Calli A. Davison-Versagli. Antioxidant compounds and their effects on ECM-detached ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2811.