NO-donating aspirin inhibits intestinal carcinogenesis in Min (APC(Min/+)) mice.

Abstract

The chemopreventive effect of nitric oxide-releasing aspirin (NO-ASA) against gastrointestinal tumorigenesis was evaluated in Min (APC(Min/+)) mice. NO-ASA consists of a traditional ASA that bears covalently attached to it an NO-releasing moiety. Four groups (N=10) of six-week-old female C57BL/6J APC(Min/+) and the corresponding C57BL/6J(+/+) wild type mice were treated either with vehicle or NO-ASA 100 mg/kg/day intrarectally for 21 days. There were no signs of overt toxicity including gastrointestinal toxicity from NO-ASA. Vehicle treated Min mice had 24.7 +/- 3.8 tumors (mean +/- SEM) and NO-ASA treated Min mice had 10.1 +/- 1.4 tumors (59% reduction; P<0.001). Wild type mice showed no tumors. NO-ASA did not affect cell proliferation in small intestinal mucosa, determined by immunohistochemical staining for PCNA. Our findings establish the strong inhibitory effect of NO-ASA in intestinal carcinogenesis in the Min mouse and suggest that this agent merits further evaluation as a chemopreventive agent against colon cancer.

• Authors: Jennie L Williams, Khosrow Kashfi, Nengtai Ouyang, Piero del Soldato, Levy Kopelovich, Basil Rigas
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 313 Issue 3 Pg. 784-8 (Jan 16 2004) ISSN: 0006-291X [Print] United States
• PMID: 14697260 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Anticarcinogenic Agents
• Proliferating Cell Nuclear Antigen
• Nitric Oxide
• Aspirin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Anticarcinogenic Agents (pharmacology)
• Aspirin (pharmacology)
• Body Weight
• Cell Division
• Colonic Neoplasms (pathology, prevention & control)
• Epithelial Cells (pathology)
• Female
• Gastrointestinal Neoplasms (prevention & control)
• Genes, APC
• Immunohistochemistry
• Intestinal Mucosa (pathology)
• Intestine, Small (pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Nitric Oxide
• Proliferating Cell Nuclear Antigen (metabolism)