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Characterization of PPARγ ligand MCC‐555 in AOM‐induced colorectal tumorigenesis
Author(s) -
Imchen Temjenmongla,
Min Kyung-Won,
Baek Seung Joon
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1050.18
Subject(s) - azoxymethane , apoptosis , aberrant crypt foci , medicine , peroxisome proliferator activated receptor , carcinogenesis , cell growth , christian ministry , survivin , cancer , cancer research , endocrinology , colorectal cancer , pharmacology , receptor , chemistry , biochemistry , colonic disease , philosophy , theology
PPARγ agonists affect cell proliferation, differentiation, and apoptosis in a PPARγ dependent and/or‐independent manner, and thereby represent a potentially important family of therapeutic compounds for cancer treatment. Dual ligands for PPARα and PPARγ, such as MCC‐555, have been developed to improve treatment of metabolic syndrome, including hyperglycemia and hyperlipidemia. Interestingly, these dual ligands also possess anti‐proliferative activities against a variety of cancer cell lines with greater potency than conventional PPARγ specific ligands. In this study, colon cancer chemopreventive properties of MCC‐555, were evaluated using azoxymethane (AOM)‐induced colonic aberrant crypt foci (ACF) in female A/J mice. 36 female mice were randomly assigned to 5 groups: (1) negative control treated with carboxymethylcellulose (vehicle); (2) positive control treated with carboxymethylcellulose plus AOM; (3) treated with 30 mg/kg MCC‐555 plus AOM; (4) treated with 60 mg/kg MCC‐555 plus AOM; (5) treated with 60 mg/kg MCC‐555. At 6 weeks of age, all animals were gavaged with carboxymethylcellulose or MCC‐555 for 5 weeks starting 1 week before initiation with AOM injection. AOM was injected i.p. once a week for 4 weeks at 10 mg/kg for groups 2, 3 and 4. Animals will be dissected, and ACF will be examined. The results will be discussed at the meeting. This work was supported by NIH grant‐R01CA108975 and University of Tennessee Center of Excellence in Livestock Diseases and Human Health grant. Temjenmongla Imchen is a recipient of National Overseas Scholarship Award [No. 11016/07/2010‐Education] from Ministry of Tribal Affairs, New Delhi, India.