Ezetimibe reverses the inhibitory effects of dietary cholesterol on mammary tumorigenesis in rats.
There are concerns regarding increased cancer incidence in patients treated with ezetimibe, an inhibitor of the absorption of dietary cholesterol. Here we tested the hypothesis that ezetimibe will accelerate mammary tumorigenesis in rats. The drug was administered at a dose of 1 ppm in an AIN-93G diet that contained 0.3% cholesterol. This experimental diet and control diets that contained either no additions or cholesterol or ezetimibe only, were fed to groups of 30 Sprague-Dawley rats 3 days after they were treated with 50 mg/kg methylnitrosourea (MNU). All rats were euthanized 22 weeks after MNU administration. Tumor multiplicity was significantly smaller in rats fed cholesterol than those fed no cholesterol (1.84 +/- 0.42 vs. 3.86 +/- 0.86 respectively, P < 0.05), but was significantly greater in the cholesterol/ezetimibe group than the group fed only cholesterol (3.48 +/- 0.59 vs. 1.84 +/- 0.42 respectively, P < 0.04). The average weight of tumors/rat was also significantly larger in the cholesterol/ezetimibe group than those fed cholesterol alone (5.67 +/- 1.15 vs. 2.56 +/- 0.71 respectively, P < 0.04). As expected, ezetimibe prevented the cholesterol raising effect of the dietary cholesterol. These results show that ezetimibe reverses the inhibitory effect of dietary cholesterol on the development of rat mammary tumors.
McNamara
Erin
E
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Archer
Michael C
MC
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D002273:Carcinogens / Q000633:toxicity; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D000069438:Ezetimibe; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D000924:Anticholesteremic Agents; D001384:Azetidines; D002273:Carcinogens; D002791:Cholesterol, Dietary; D008770:Methylnitrosourea; D000069438:Ezetimibe