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

Biochem Biophys Res Commun. 2004 Jan 16;313(3):784-8. doi: 10.1016/j.bbrc.2003.12.015.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anticarcinogenic Agents / pharmacology
  • Aspirin / pharmacology*
  • Body Weight
  • Cell Division
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / 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


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