Nitric-oxide-donating aspirin (NO-ASA), consisting of ASA (aspirin) plus an -ONO2 moiety linked to it via a molecular spacer, is a new drug for cancer prevention. NO-ASA seems to overcome the low potency and toxicity of traditional ASA. The -ONO2 moiety is responsible for releasing NO, and it appears to be required for biological activity. In studies in vitro, NO-ASA inhibits the growth of colon, pancreatic, prostate, lung, skin, leukaemia and breast cancer cells, and is up to 6000-fold more potent than traditional ASA. This effect is owing to cell kinetics [inhibition of proliferation, induction of apoptosis (multiple criteria) and blocking the G1 to S cell-cycle transition] and cell signalling [inhibition of Wnt signalling (IC50=0.2 μM), inhibition of NF-κB (nuclear factor κB) activation (IC50=7.5 μM), inhibition of nitric oxide synthase-2 expression (IC50=48 μM), inhibition of MAPK (mitogen-activated protein kinase) signalling (IC50=10 μM) and induction of cyclo-oxygenase-2 at approx. 10 μM]. In studies in vivo, NO-ASA inhibits intestinal carcinogenesis in Min mice (tumour multiplicity was reduced by 59% after 3 weeks, with no effect in control animals and no side effects) and in the N-nitrosobis(2-oxopropyl)amine model of pancreatic cancer, where there was an 89% reduction in NO-ASA (3000 p.p.m. in the diet)-treated animals (P<0.001). There was no statistically significant effect by traditional ASA at equimolar doses. Our data indicate that NO-ASA is a highly promising agent for the prevention and/or treatment of cancer.
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Conference Article|
August 01 2005
Molecular targets of nitric-oxide-donating aspirin in cancer
K. Kashfi;
K. Kashfi
1
*Department of Physiology and Pharmacology, City University of New York Medical School, NY 10031, U.S.A.
1To whom correspondence should be addressed (email kashfi@med.cuny.edu).
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B. Rigas
B. Rigas
†Department of Medicine, State University of New York at Stony Brook, NY 11794, U.S.A.
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Publisher: Portland Press Ltd
Received:
March 22 2005
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (4): 701–704.
Article history
Received:
March 22 2005
Citation
K. Kashfi, B. Rigas; Molecular targets of nitric-oxide-donating aspirin in cancer. Biochem Soc Trans 1 August 2005; 33 (4): 701–704. doi: https://doi.org/10.1042/BST0330701
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