Modulation of angiogenesis by omega-3 polyunsaturated fatty acids is mediated by cyclooxygenases.
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 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 omega-3 PUFAs in cancer suppression is angiogenesis, a process of new blood vessel formation within rapidly growing tumors. Here, we demonstrate that omega-6 PUFAs stimulate and omega-3 PUFAs inhibit major proangiogenic 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 omega-6 PUFA arachidonic acid. The cyclooxygenase (COX)-mediated conversion of PUFAs 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 PUFAs undergo biotransformation by COX-2 to lipid mediators that modulate tumor angiogenesis, which provides new insight into the beneficial effects of omega-3 PUFAs.
Szymczak
Melissa
M
Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, Camperdown, Australia.
Murray
Michael
M
Petrovic
Nenad
N
D000527:Alprostadil / Q000031:analogs & derivatives / Q000378:metabolism; D042702:Angiopoietin-2 / Q000096:biosynthesis; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism*
D042702:Angiopoietin-2; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid; C033246:prostaglandin E3; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020780:Matrix Metalloproteinase 9; D000527:Alprostadil; D015232:Dinoprostone