Modulation of angiogenesis by ω-3 polyunsaturated fatty acids is mediated by cyclooxygenases
Open Access
- 1 April 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 111 (7), 3514-3521
- https://doi.org/10.1182/blood-2007-08-109934
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 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 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.Keywords
This publication has 38 references indexed in Scilit:
- CD13/APN regulates endothelial invasion and filopodia formationBlood, 2007
- Regulation of endothelial cell migration by amphiphiles—are changes in cell membrane physical properties involved?Angiogenesis, 2007
- Inhibition of Cytokine Signaling in Human Retinal Endothelial Cells through Modification of Caveolae/Lipid Rafts by Docosahexaenoic AcidInvestigative Opthalmology & Visual Science, 2007
- The "chemoinvasion assay": a tool to study tumor and endothelial cell invasion of basement membranesThe International Journal of Developmental Biology, 2004
- Free fatty acids trigger apoptosis and inhibit cell cycle progression in human vascular endothelial cellsThe FASEB Journal, 2003
- N‐3 and N‐6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case‐control study in Tours, FranceInternational Journal of Cancer, 2001
- Structure of Eicosapentaenoic and Linoleic Acids in the Cyclooxygenase Site of Prostaglandin Endoperoxide H Synthase-1Published by Elsevier ,2001
- Cyclooxygenase-2 Expression in Lipopolysaccharide-Stimulated Human Monocytes Is Modulated by Cyclic AMP, Prostaglandin E2, and Nonsteroidal Anti-inflammatory DrugsBiochemical and Biophysical Research Communications, 2000
- The role of NF-κB/IκB proteins in cancer: implications for novel treatment strategiesSurgical Oncology, 1999
- The Composition of Food Consumed by Greenland EskimosActa Medica Scandinavica, 1976