(12-02-08) Modulation of angiogenesis by {omega}-3 polyunsaturated fatty acids is mediated by cyclooxygenases.

Szymczak M, Murray M, Petrovic N.

Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia.

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 (omega-3 PUFA), 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 omega-3 PUFA in cancer suppression is angiogenesis, a process of new blood vessel formation within rapidly growing tumors. Here, we demonstrate that omega-6 PUFA stimulate and omega-3 PUFA inhibit major pro-angiogenic processes in human endothelial cells, including the induction of angiopoietin-2 and matrix metalloprotease-9, endothelial invasion and tube formation that are usually activated by the major omega-6 PUFA arachidonic acid. The cyclooxygenase (COX)-mediated conversion of PUFA to prostanoid derivatives participated in modulation of the expression of Ang2. Thus, the omega-6 PUFA-derived prostaglandin E2 augmented, whereas the omega-3 PUFA-derived prostaglandin E3 suppressed the induction of Ang2 by growth factors. Our findings are consistent with the suggestion that PUFA undergo biotransformation by COX-2 to lipid mediators that modulate tumor angiogenesis which provides new insight into the beneficial effects of omega-3 PUFA.

Source: Blood. 2008 Jan 23

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