Characterization of PPAR dual ligand MCC-555 in AOM-induced colorectal tumorigenesis.

Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers. Peroxisome proliferator-activated receptor γ (PPARγ) agonists represent a potentially important family of chemopreventive/therapeutic compounds for cancer treatment by affecting cell proliferation, differentiation, and apoptosis. Dual ligands for PPARα and PPARγ, such as netoglitazone (MCC-555), have been developed to improve treatment of metabolic syndromes, including hyperglycemia and hyperlipidemia. Interestingly, these dual ligands also possess anti-proliferative activities against a variety of cancer cell lines with a greater potency than conventional PPARγ specific ligands. In this study, chemopreventive properties of MCC-555 in colorectal tumorigenesis were evaluated using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in A/J mice. We found that MCC-555 suppressed AOM-induced ACF in A/J mice, compared to the control group. Administration of MCC-555 resulted in decreased mitoses and increased apoptotic cells in the colon. Furthermore, expression of tumor suppressor protein MUC2 was increased in MCC-555 treated mice. Our data clearly suggest that MCC-555 has an effect on the early events of colon carcinogenesis, thus providing evidence that MCC-555 could be a potential preventive compound for CRC.

• Authors: Temjenmongla Imchen, Jorden Manasse, Kyung-Won Min, Seung Joon Baek
• Journal: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie (Exp Toxicol Pathol) Vol. 65 Issue 6 Pg. 919-24 (Sep 2013) ISSN: 1618-1433 [Electronic] Germany
• PMID: 23369238 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier GmbH. All rights reserved.

Chemical References

• Antineoplastic Agents
• Muc2 protein, mouse
• Mucin-2
• PPAR gamma
• Thiazolidinediones
• Azoxymethane
• netoglitazone

Topics

• Aberrant Crypt Foci (chemically induced, metabolism, pathology, prevention & control)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Azoxymethane (toxicity)
• Colorectal Neoplasms (chemically induced, metabolism, pathology, prevention & control)
• Dose-Response Relationship, Drug
• Female
• Mice
• Mice, Inbred Strains
• Mitosis (drug effects)
• Mucin-2 (biosynthesis)
• PPAR gamma (agonists)
• Thiazolidinediones (administration & dosage, pharmacology, therapeutic use)