Cyclooxygenase-independent chemoprevention with an aspirin derivative in a rat model of colonic adenocarcinoma

doi:10.1016/S0024-3205(98)00191-X

Life Sciences

Volume 62, Issue 23, 1 May 1998, Pages 367-373

https://doi.org/10.1016/S0024-3205(98)00191-X Get rights and content

Abstract

Aspirin decreases the risk of colorectal cancer, reportedly through suppression of cyclooxygenase (COX) activity. Using a rat model of colonic adenocarcinoma, we compared the chemopreventative effects of aspirin versus a nitric oxide-releasing derivative (NCX-4016) which does not inhibit COX. Beginning six weeks after intracolonic administration of trinitrobenzene sulfonic acid, the rats were given azoxymethane weekly (15 mg/kg i.p.) for 4 weeks. Over the same 4-week period, the rats were treated daily with vehicle, aspirin (10 mg/kg) or NCX-4016 (equimolar dose). Six weeks later, the number of aberrant crypt foci (an early preneoplastic lesion) were blindly counted by light microscopy. Effects of aspirin vs. NCX-4016 on COX-1 and COX-2 activity were compared, as was their analgesic activity Rats receiving vehicle developed a mean of 856 ± 260 aberrant crypt foci in the colon. Aspirin reduced the number of aberrant crypt foci by 64%, while NCX-4016 produced an 85% reduction. Aspirin, but not NCX-4016, markedly suppressed systemic COX-1 and COX-2 activity, and colonic prostaglandin synthesis. Despite not inhibiting COX, NCX-4016 exhibited comparable analgesic activity to aspirin. These results demonstrate that NCX-4016, a nitric oxide-releasing aspirin derivative, exhibited superior chemopreventative effects to aspirin in this model of colon cancer. This effect occurred independent of inhibition of COX-1 or COX-2.

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Pharmacology letter Accelerated communicationCyclooxygenase-independent chemoprevention with an aspirin derivative in a rat model of colonic adenocarcinoma

Abstract

Cell

Gastroenterology

Gastroenterology

Biochem. Pharmacol.

Gastroenterology

Gastroenterology

Thromb. Res.

Arch. Biochem. Biophys.

J. Natl. Cancer Inst.

Ann. Intern. Med.

New Engl. J. Med.

Ann. Med.

Gut

J. Clin. Invest

Cancer Res.

Pharmacology letter Accelerated communication
Cyclooxygenase-independent chemoprevention with an aspirin derivative in a rat model of colonic adenocarcinoma