Modulation of angiogenesis by ω-3 polyunsaturated fatty acids is mediated by cyclooxygenases

Abstract

The potential role of dietary fats in cancer is attracting considerable interest within the community. Both epidemiologic and experimental findings suggest that omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which are almost absent from typical Western diets, exert protective effects against cancer progression, although the precise mechanism of this suppression remains unknown. One of the potential targets for ω-3 PUFAs in cancer suppression is angiogenesis, a process of new blood vessel formation within rapidly growing tumors. Here, we demonstrate that ω-6 PUFAs stimulate and ω-3 PUFAs inhibit major proangio-genic processes in human endothelial cells, including the induction of angiopoietin-2 (Ang2) and matrix metalloprotease-9, endothelial invasion, and tube formation, that are usually activated by the major ω-6 PUFA arachidonic acid. The cyclooxygenase (COX)- mediated conversion of PUFAs to prostanoid derivatives participated in modulation of the expression of Ang2. Thus, the ω-6 PUFA-derived prostaglandin E2 augmented, whereas the ω-3 PUFA-derived prostaglandin E3 suppressed the induction of Ang2 by growth factors. Our findings are consistent with the suggestion that PUFAs undergo biotransformation by COX-2 to lipid mediators that modulate tumor angiogenesis, which provides new insight into the beneficial effects of ω-3 pufas. © 2008 by The American Society of Hematology.