Cytosolic fatty acid synthesis and mitochondrial fatty acid oxidation coexist simultaneously in breast cancer cells

Abstract

The survival and proliferation of cancer cells depends on fatty acid synthesis and oxidation. The aim of this study was to evaluate existence of simultaneous cytosolic fatty acid synthesis (FAS) and mitochondrial fatty acid oxidation (FAO) In breast cancer cells. Metabolic flux analysis using 13Clabeled glutamine in combination with gene silencing using small interfering RNAS (siRNAs) against FASN, ECHS1 and ME genes. The simultaneous occurence of both processes implies that part of the acetyl-CoA feeding the TCA cycle is derived from citrate production in 5 labeled carbons (MS isotopomer). If these lipids are being simultaneously degraded, labeled acetyl-CoA will be entering the TCA cycle, resulting in the formation of fully labeled citric acid molecules (M6 isotopomer). The results showed that BCC (breast cancer cells) had the higher amount of fully labelled citrate (M6 isotopomer), than MCF7 (human breast adenocarcinoma cell line) and BT-474 (human breast ductal carcinoma cell line) cells. [...].