Alterations in PAF Synthesis by N-3 Fatty Acids

Wake Forest University Health Sciences, Winston-Salem NC

Investigators

Linked publications & trials

Abstract

Prostate cancer incidence is reduced in men who consume increased amounts of n-3 fatty acids (versus n-6 fatty acids) and this observation has led to the suggestion that these fatty acids are useful dietary supplements to prevent cancer and reduce its recurrence. Since both the n-3 and n-6 are essential fatty acids, their relative levels in tissues are totally controlled by diet. The membranes of mammalian cells are composed of an array of phospholipid species that are now recognized to function as a diverse source of lipid mediators. These mediators function as both intercellular and intracellular signals and are key components of signaling cascades. Arachidonic acid (AA),an n-6 fatty acid, is the major precursor for prostaglandins and leukotrienes in people consuming a typical "Western diet". However, when the diet is enriched in n-3 fatty acids the synthesis of lipid mediators is markedly altered. The levels of ether-linked phospholipids vary greatly among cells; but, in a number of cells they are known to serve as an important reservoir of AA and as a precursor of platelet activating factor (PAF), one of the most active mediators known. When the diet is rich in n-3 fatty acids the levels of AA in the ether-linked lipids is reduced. We hypothesize that supplementation of cells with n-3 fatty acids will result in lipid alterations that decrease PAF precursors and thus PAF synthesis. Our specific aims are: (1) to determine the effect of n-3 fatty acid supplementation on the synthesis of PAF and eicosanoids; (2) to determine if n-3 fatty acid-altered PAF synthesis alters the growth of prostate cancer cells in vitro; and (3) to determine if n-3 fatty acid-altered synthesis of PAF and eicosanoids alters the growth of prostate cancer cells in vivo. The proposed studies promise to advance our understanding of the role of n-3 fatty acids in tumor cells and could lead to new therapeutic approaches and targets.