Abstract 3353: Docosahexaenoic acid enhances 2-deoxyglucose treatment in breast and lung cancer cells in vitro

Abstract

Abstract Increased aerobic glycolysis is a common phenotype of cancer cells and is known as the Warburg effect. Recent studies have focused on targeting cellular metabolism to impede cancer cell growth. Previous findings in our laboratory have demonstrated that docosahexaenoic acid (DHA; C22:6 n-3), a long-chain omega-3 polyunsaturated fatty acid (PUFA), can inhibit cancer cell metabolism and reduce intracellular ATP levels. This study investigated the effects of concurrent treatment with DHA with 2-deoxyglucose (2DG), an inhibitor of glucose metabolism, in multiple cancer cell models in vitro, BT-474 human breast ductal carcinoma, MDA-MB-231 human breast adenocarcinoma, and A549 human lung adenocarcinoma. Dose-dependent decreases in intracellular ATP levels were observed with DHA and 2DG, both alone and in combination. In addition to the significant decreases in ATP levels, large decreases in extracellular lactate concentrations were observed in all three cell lines as well, suggesting that the combination of 2DG and DHA can augment treatment, mimic glucose deprivation and play a role in reducing the Warburg effect. Moreover, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were significantly reduced with the combination of DHA and 2DG, which suggests that the combination of DHA with other metabolic inhibitors, like 2DG, may sensitize cells to current treatment. Our findings show that combining DHA with 2DG enhances the efficacy of 2DG treatment alone, which may help to reduce the cytotoxic effects by 2DG on normal cells. Other metabolic inhibitors are being employed in combination with DHA to determine the mechanisms behind the DHA-induced sensitizing effects, which will provide additional treatment strategies for oncologists and cancer patients. Citation Format: Michael Mouradian, Irvin V. Ma, Erika D. Vicente, Amy M. Chattin, Ronald S. Pardini. Docosahexaenoic acid enhances 2-deoxyglucose treatment in breast and lung cancer cells in vitro. [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 3353. doi:10.1158/1538-7445.AM2014-3353