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.