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.
Keywords: ACF; ANOVA; AOM; Aberrant crypt foci; Azoxymethane; CMC; CRC; Colon cancer; H&E; MCC-555; PPAR; PPAR ligand; TUNEL; TdT; TdT-mediated deoxyuridine triphosphate nick-end labeling; aberrant crypt foci; analysis of variance; azoxymethane; carboxyl methyl cellulose; colorectal cancer; hematoxylin and eosin; peroxisome proliferator-activated receptor; terminal deoxynucleotidyl transferase.
Copyright © 2013 Elsevier GmbH. All rights reserved.