Abstract 2920: Effect of nitric oxide on invasiveness and metabolism of cancer cells.

Abstract

Abstract Nitric oxide synthase (NOS) expression has been shown to be upregulated in cancer cells compared to normal cells. The resulting increased nitric oxide (NO) production changes the metastatic ability of cancer cells. The link between NOS expression, NO production, apoptosis, and drug resistance in ovarian cancer is beginning to be studied. However, the effect of NO on metabolism and invasiveness of ovarian cancer cells is not known. Here, using gas chromatography - mass spectroscopy based isotope analysis we show that highly-invasive ovarian cancer cells convert arginine to citrulline via the nitric oxide pathway as opposed to less-invasive ovarian cancer cells. We hypothesize that NO is important for the proliferation, migration, invasion, and drug resistance in highly-invasive ovarian cancer cells as opposed to less-invasive ovarian cancer cells, and that these changes in metastatic behavior are linked to changes in metabolism. We show that L-NG-Nitroarginine Methyl Ester (L-NAME), an inhibitor of NOS, decreases NO production and thus decreases proliferation, migration, and invasion of ovarian cancer cells, as well as decreases drug resistance. Using metabolic assays, we show that NO affects the glucose consumption, lactate secretion, and pyruvate uptake, and provides us with clues regarding the effect of NO on glycolytic activity of highly-invasive and less-invasive ovarian cancer cells. Lastly, we show that NO affects oxygen consumption rate in these cells, and thus oxidative phosphorylation. Our findings are the first to link NO production and invasiveness with metabolism in ovarian cancer cells. Citation Format: Christine A. Caneba, Juan Marini, Deepak Nagrath. Effect of nitric oxide on invasiveness and metabolism of cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2920. doi:10.1158/1538-7445.AM2013-2920