Omega-3 Fatty Acids and PPARγ in Cancer

Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γ and, due to the effects of PPARγ on cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal models. In vitro studies have shown that omega-3 PUFAs inhibit cell proliferation and induce apoptosis in cancer cells through various pathways but one of which involves PPARγ activation. The differential activation of PPARγ and PPARγ-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relating PUFAs to PPARγ and cancer and offers a new paradigm relating an n-3 PUFA through PPARγ to the expression of the cell surface proteoglycan, syndecan-1, and to the death of cancer cells.