Translational regulation of gene expression by ω-3 fatty acids

The incidence of some cancers shows dramatic variations around the world that cannot be explained by ethnic or racial differences. Observational studies point to a negative correlation between consumption of fish and incidence of breast and prostate cancer. In vitro and animal model studies indicate that (omega-3) PUFAs present at high concentrations in marine animals inhibit proliferation of cancer cells and growth of tumors. However, how these fatty acids inhibit cell proliferation and tumor growth is a matter of considerable debate. In this review we summarize our recent work indicating that Ca++ depletion mediated phosphorylation of the alpha subunit of elF2 and subsequent inhibition of translation initiation account for the anti-cancer activity of (omega-3) PUFAs.