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 microM), inhibition of
NF-kappaB (
nuclear factor kappaB) activation (IC50=7.5 microM), inhibition of
nitric oxide synthase-2 expression (IC50=48 microM), inhibition of MAPK (
mitogen-activated protein kinase) signalling (IC50=10 microM) and induction of cyclo-oxygenase-2 at approx. 10 microM]. 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.