Dose-dependent effects of dietary phytosterol on epithelial cell proliferation of the murine colon

Abstract

Phytosterols are a group of compounds in plants that have been found to inhibit tumour development and decrease enhanced colonic epithelial cell proliferation in carcinogen-treated rats. The mechanism by which phytosterols may inhibit tumour development and alter cell proliferation is unknown. However, studies have shown that dietary phytosterol intake may alter levels of certain promoters in the colonic lumen, leading to altered levels of colonic epithelial cell proliferation. In this study, the effect of dietary phytosterol on the proliferative status of the intestinal epithelium was investigated in mice. Inbred C57BI/6J mice were fed semi-synthetic diet (control); 0.1% cholic acid, 0% phytosterol (cholic acid control); and cholic acid plus 0.3, 1.0 or 2.0% phytosterol. Dietary cholic acid significantly increased colonic epithelial cell proliferation and the highest labelled cell position by 92 and 35%, respectively. Phytosterol significantly reduced the enhanced labelling index and the position of the highest labelled cell in a dose-dependent manner. Mitotic index was also reduced significantly by phytosterol but not in a dose-dependent manner. The results of this study indicate that phytosterol influences the colonic epithelial cell morphometrics, that are important preneoplastic events in colon carcinogenesis, and may thus contribute to a reduced risk of cancer.