Studies on the Chemopreventive Effect of Carnitine on Tumorigenesis In Vivo, Using Two Experimental Murine Models of Colon Cancer

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 multi-ciplicity (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.