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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3514-3521. Prepublished online as a Blood First Edition Paper on January 23, 2008; DOI 10.1182/blood-2007-08-109934. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-08-109934v1 111/7/3514    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Szymczak, M. Articles by Petrovic, N. Search for Related Content PubMed PubMed Citation Articles by Szymczak, M. Articles by Petrovic, N. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 29, 2007 Accepted January 3, 2008 Modulation of angiogenesis by -3 polyunsaturated fatty acids is mediated by cyclooxygenases Melissa Szymczak, Michael Murray, and Nenad Petrovic* Pharmacogenomics and Drug Development Group, Faculty of Pharmacy, University of Sydney, Sydney, NSW, Australia * Corresponding author; email: npetrovic{at}usyd.edu.au. 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 (-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 -3 PUFA in cancer suppression is angiogenesis, a process of new blood vessel formation within rapidly growing tumors. Here, we demonstrate that -6 PUFA stimulate and -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 -6 PUFA arachidonic acid. The cyclooxygenase (COX)-mediated conversion of PUFA to prostanoid derivatives participated in modulation of the expression of Ang2. Thus, the -6 PUFA-derived prostaglandin E2 augmented, whereas the -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 -3 PUFA. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Zhao, D. Wang, S. Y. Cheranov, M. Karpurapu, K. R. Chava, V. Kundumani-Sridharan, D. A. Johnson, J. S. Penn, and G. N. Rao A novel role for activating transcription factor-2 in 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis J. Lipid Res., March 1, 2009; 50(3): 521 - 533. [Abstract] [Full Text] [PDF]

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