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.
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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)
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Copyright | Copyright © 2013 Elsevier GmbH. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Muc2 protein, mouse
- Mucin-2
- PPAR gamma
- Thiazolidinediones
- Azoxymethane
- netoglitazone
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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)
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