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Integrative Medicine
> Aspirin
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The FASEB Journal. 2006 Oct;20:2009-2016
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Abstract |
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Therapeutic levels of aspirin and
salicylate directly inhibit a model of angiogenesis through a
Cox-independent mechanism
Gillian M. Borthwick*,1,
A. Sarah Johnson1,
Matthew Partington*,
John Burn*, Robert
Wilson† and Helen M.
Arthur*,2
*Institute of Human
Genetics, International Centre for Life, University of Newcastle,
Newcastle upon Tyne, UK; and †Department of Surgery, James Cook
Hospital, University of Durham, Durham, UK. 2Correspondence:
Institute of Human Genetics, International Centre for Life, University
of Newcastle, NE1 3BZ, UK. E-mail helen.arthur@ncl.ac.uk
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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.
Key Words: endothelial cells,
Celecoxib, SC560, cancer
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© 2006 by The Federation of American
Societies for Experimental Biology.
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