Modulation of angiogenesis by omega-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 (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.

• Authors: Melissa Szymczak, Michael Murray, Nenad Petrovic
• Journal: Blood (Blood) Vol. 111 Issue 7 Pg. 3514-21 (Apr 01 2008) ISSN: 0006-4971 [Print] United States
• PMID: 18216296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-2
• Fatty Acids, Omega-3
• Fatty Acids, Omega-6
• Arachidonic Acid
• prostaglandin E3
• Cyclooxygenase 2
• PTGS2 protein, human
• Matrix Metalloproteinase 9
• Alprostadil
• Dinoprostone

Topics

• Alprostadil (analogs & derivatives, metabolism)
• Angiopoietin-2 (biosynthesis)
• Arachidonic Acid (metabolism)
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Endothelial Cells (enzymology, pathology)
• Fatty Acids, Omega-3 (metabolism, pharmacology)
• Fatty Acids, Omega-6 (metabolism, pharmacology)
• Humans
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasms (drug therapy, enzymology, pathology)
• Neovascularization, Pathologic (drug therapy, metabolism)