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Therapeutic levels of aspirin and salicylate directly inhibit a model of angiogenesis through a Cox-independent mechanism

Lookup NU author(s): Dr Gillian Borthwick, Dr Sarah Johnson, Professor Sir John Burn, Professor Helen Arthur

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Abstract

A range of antineoplastic properties is attributed to aspirin, thought to be due to inhibition of cyclooxygenase (Cox) enzymes in tumor cells. One important outcome is that by reducing angiogenic factor secretion by cancer cells, aspirin also inhibits angiogenesis, thereby restricting tumor growth. However, aspirin may also have direct effects on endothelial cells to regulate angiogenesis. Our aim was to quantitate these effects and determine whether they occurred through inhibiting Cox enzymes. The effects of aspirin, salicylate (the natural deacetylated form of aspirin), and the selective Cox inhibitors SC560 and Celecoxib on endothelial cell proliferation, viability, and angiogenesis were compared. Therapeutic aspirin concentrations (0.5 mM) had no detectable effect on endothelial cell viability or proliferation but caused a striking reduction in tubule formation in a three-dimensional collagen angiogenesis assay. This was also seen with equimolar concentrations of salicylate, while selective Cox inhibitors did not inhibit angiogenesis in this assay either alone or in combination. Furthermore, high doses of aspirin or salicylate (5 mM), well above therapeutic plasma concentrations, lead to endothelial cell apoptosis. We conclude that aspirin, at therapeutic concentrations, directly inhibits angiogenesis via a Cox-independent mechanism, which may significantly contribute to its neoplastic protective effects. © FASEB.


Publication metadata

Author(s): Borthwick GM, Johnson AS, Partington M, Burn J, Wilson R, Arthur HM

Publication type: Article

Publication status: Published

Journal: The FASEB Journal

Year: 2006

Volume: 20

Issue: 12

Pages: 2009-2016

ISSN (print): 0892-6638

ISSN (electronic): 1530-6860

Publisher: Federation of American Societies for Experimental Biology

URL: http://dx.doi.org/10.1096/fj.06-5987com

DOI: 10.1096/fj.06-5987com

PubMed id: 17012253


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