Omega-3 but Not Omega-6 Unsaturated Fatty Acids Inhibit the Cancer-Specific ENOX2 of the HeLa Cell Surface with No Effect on the Constitutive ENOX1

Abstract

ABSTRACT.Epidemiological and laboratory studies suggest that dietary fatty acids (oleic acid (in olive oil), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) (in fish oil)) play important roles in carcinogenesis. The most potent antitumor effects of all fatty acids are given by fatty acid conjugated linoleic acid (CLA). The antitumor effects of CLA may be mediated through enhanced apoptosis. While CLA, EPA, and DHA (omega-3 polyunsaturated fatty acids) have inhibitory effects on cancer cells, omega-6 fatty acids have often shown negative or potentiating effects on cancer cells. Linoleic acid (an omega-6) is desaturated in the cell by delta 6 and 5 destaturases to form arachidonic acid. COX 1 and 2 isoforms then act on arachidonic acid to form prostaglandins and other related regulatory molecules. It is normally thought that what is important to the development of the cancerous phenotype is some balance of these various metabolites. In experiments with surface NOX proteins released from HeLa cells, spectrophotometric measurements of the oxidation of NADH revealed inhibition of the cancer-specific ENOX2 activity by CLA and the omega-3 fatty acids, eicosapentaenoic, docosahexaenoic, and α-linolenic acids. The constitutive ENOX1 activity was not inhibited. In contrast, the omega-6 fatty acids, linoleic acid, and arachidonic acid inhibited neither ENOX1 nor ENOX2. The findings indicate the possibility that a direct effect of CLA and omega-3 fatty acids on ENOX2 may be responsible for the potent activity of CLA and omega-3 fatty acids in cancer prevention and therapy.