Chemoprevention of colon cancer carcinogenesis by balsalazide: inhibition of azoxymethane-induced aberrant crypt formation in the rat colon and intestinal tumor formation in the B6-Min/+ mouse.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin have been shown to suppress colon carcinogenesis and in some cases reduce the size of colorectal polyps. Balsalazide disodium (BSZ) is a colon-specific prodrug of the salicylate, 5-aminosalicylic acid. The aim of the present study was to test the chemopreventive activity of BSZ in two established animal models of colon tumorigenesis, azoxymethane-induced aberrant crypt formation in the rat and intestinal tumor formation in the B6-Min/+ mouse. Aberrant crypt foci (ACF) were induced in Fischer 344 rats via 2 subcutaneous injections of azoxymethane (20 mg/kg). BSZ was supplied in the drinking water for 8 weeks and ACF quantitated. B6-Min/+ mice were treated from 55 days of age for 90 days and intestinal tumors scored for number, size and location. BSZ treatment of AOM-injected rats reduced ACF formation in a dose-dependent manner by 60% with the greatest effect observed on ACF with 4 or more crypts. In B6-Min/+ mice a dose-dependent reduction of intestinal tumor number was observed which reached 80% in the distal small intestine and colon. A preliminary mechanistic study in cultured human colon cancer cells showed that both BSZ and 5-ASA inhibited colon cancer cell proliferation in vitro. However, 5-ASA but not BSZ produced changes consistent with the induction of apoptosis. BSZ produces a dose-dependent chemopreventive effect on colon carcinogenesis. A possible mechanism is consistent with the inhibition of cellular proliferation and the induction of apoptosis.

• Authors: D J MacGregor, Y S Kim, M H Sleisenger, L K Johnson
• Journal: International journal of oncology (Int J Oncol) Vol. 17 Issue 1 Pg. 173-9 (Jul 2000) ISSN: 1019-6439 [Print] Greece
• PMID: 10853036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Aminosalicylic Acids
• Anti-Ulcer Agents
• Anticarcinogenic Agents
• Phenylhydrazines
• Prodrugs
• Mesalamine
• Azoxymethane
• balsalazide
• Indomethacin

Topics

• Aminosalicylic Acids (pharmacology, toxicity)
• Animals
• Anti-Ulcer Agents (pharmacology)
• Anticarcinogenic Agents (pharmacology)
• Azoxymethane (toxicity)
• Cell Division (drug effects)
• Colonic Neoplasms (chemically induced, pathology, prevention & control)
• Genes, APC
• Humans
• Indomethacin (toxicity)
• Intestinal Mucosa (drug effects, pathology)
• Intestinal Neoplasms (chemically induced, pathology, prevention & control)
• Mesalamine (toxicity)
• Mice
• Mice, Mutant Strains
• Phenylhydrazines
• Prodrugs (toxicity)
• Rats
• Rats, Inbred F344
• Tumor Cells, Cultured