Abstract 5154: Fatty acids mediated regulation of cancer metabolism

Although fatty acids have been shown to modulate progression, growth and invasiveness of cancer cells, it remains unclear how saturated and unsaturated fatty acids affect metabolic reprogramming of aggressive and nonaggressive cancer metabolism. In this study, we tested the hypothesis that fatty acids induce differential competitive effects on glucose oxidation in aggressive and nonaggressive ovarian cancer cells. Normal cells rely mainly on mitochondrial oxidative phosphorylation for their required energy supply, however, cancer cells utilize aerobic glycolysis pathway for their energetic need. We hypothesized that high fat diet could deregulate this metabolic alteration in cancer cells. Such as glucose, fatty acids are an influential source of ATP, energy currency, within a cell. In our study, using metabolic footprinting we studied the affect of both saturated (stearic and palmitic acid) and unsaturated fatty acids (linoleic and oleic) on glycolysis, pentose phosphate pathway and TCA cycle. Moreover, we also studied the effect of glucose on fatty acid oxidation, uptake and endogenous fatty acid synthesis. Metabolic flux analysis was done for comparative metabolic profiling under various nutritional conditions. We observed that fatty acids differentially regulate highly invasive ovarian cancer (SKOV3 and SKOV3ip) cells than less invasive ovarian cancer (OVCAR3) cells. Interestingly, we found strong effect of fatty acids on glycolysis in less invasive cancer cells. In contrast, our study showed that glucose has dominant effect on aggressive cells compared to less aggressive cells. Our studies emphasize the role of fatty acids in ovarian cancer growth, invasion and migration and underlie the need to develop therapy based on high fat diet synergistically with existing chemotherapeutics and cancer drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5154. doi:1538-7445.AM2012-5154