title: Studies on the chemopreventive effect of carnitine on tumorigenesis in vivo, using two experimental murine models of colon cancer.
abstract: Carnitine is known for its essential role in intermediary metabolism. In vitro studies suggest that its antioxidant and anti-inflammatory properties are potentially beneficial toward cancer prevention. This study tested effects of carnitine on the development of colon cancer in vivo using 2 murine models: azoxymethane (AOM) treatment as a model of carcinogen-induced colon cancer and a genetically induced model using Apc (Min/+) mice. AOM and Apc (Min/+) mice divided into dietary groups varying in lipid content, with or without carnitine supplementation (0.08%). AOM-exposed mice on a high butterfat diet had significantly increased aberrant crypts (ACF) (9.3 ± 0.88 vs. 6.3 ± 0.65), and macroscopic tumors (3.8 ± 0.95 vs. 2.0 ± 0.25) compared to mice on a control diet. In AOM mice fed the high butterfat diet, carnitine supplementation inhibited ACF (4.9 ± 0.7 vs. 9.3 ± 0.88, P < 0.001), crypt multiciplicity (1.6 ± 0.08 vs. 1.92 ± 0.1, P < 0.01) and tumors (1.5 ± 0.38 vs. 3.8 ± 0.95, P < 0.001). Carnitine supplementation resulted in significantly increased tissue carnitine and acylcarnitine levels. Carnitine inhibited the development of precancerous lesions and macroscopic colonic tumors in AOM-treated mice. However, carnitine did not exert protective effects on intestinal tumors in Apc (Min/+) mice.
authors.affiliation: Division of Gastroenterology, Research Institute, McGill University Health Center, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Dionne
authors.forename: Ihsan
authors.initials: I
authors.lastname: Elimrani
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Roy
authors.forename: Ijaz A
authors.initials: IA
authors.lastname: Qureshi
authors.forename: Dittakavi R
authors.initials: DR
authors.lastname: Sarma
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D002331:Carnitine / Q000032:analysis / Q000494:pharmacology*; D002332:Carnitine O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D004195:Disease Models, Animal; D017491:Genes, APC; D007422:Intestines / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation
chemical_list: D016588:Anticarcinogenic Agents; D002332:Carnitine O-Acetyltransferase; D001397:Azoxymethane; D002331:Carnitine