Omega-3 Fatty Acids in Cancer Prevention and Control: A Membrane Perspective
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Springer Science+Business Media New York 2013. Long-chain n-3 polyunsaturated fatty acids (PUFA) have been shown to provide health benefits in a number of diseases including several forms of cancer. In this chapter we will discuss in detail some of the prominent mechanisms through which n-3 PUFA and its metabolites are believed to function in the prevention of colon tumorigenesis. At the plasma membrane, n-3 PUFA antagonize the production of inflammatory and procarcinogenic n-6 PUFA (i.e., arachidonic acid)-derived metabolites. Additionally, the highly unsaturated nature of n-3 PUFA impacts cell membrane properties and dynamics thereby altering numerous cellular functions, including intracellular signaling, cell growth, survival, and proliferation. Due to the sterically incompatible relationship between docosahexaenoic acid, sphingolipids, and cholesterol, the major constituents of lipid rafts, n-3 PUFA modulate these crucial membrane microdomains and perturb efficient signal transduction thereby eliciting the same biological effects exploited by some anti-cancer therapies. Moreover, we discuss how alterations in lipid rafts and downstream signaling impact both epithelial cells and the activation of immune cells. This is noteworthy, because chronic inflammation plays a critical role in tumorigenesis. Therefore, we also present an overview regarding the anti-inflammatory and immunomodulatory mechanisms through which n-3 PUFA perturb the tumor microenvironment and downregulate the activation of critical transcription factors and target genes with an established role in cancer development. Finally, we discuss recent evidence suggesting that n-3 PUFA in combination with other dietary bioactive nutrients, such as soluble fiber and curcumin, could be beneficial in cancer prevention. Collectively, we demonstrate that dietary n-3 PUFA have utility in the prevention of cancer development through mechanisms centered at both the molecular, cellular (plasma membrane), and tissue level.