The role of vitamin D in normal and pathologic processes in the colon.

Vitamin D(3) metabolites and analogues have recently been shown to play an important role in the regulation of a number of important cellular processes, including proliferation, differentiation, and apoptosis, in addition to their established roles in mineral homeostasis. The actions of these secosteroids involve both rapid, nongenomic effects and genomic effects; the latter mediated via the vitamin D receptor and other transcription factors. Their effects have been described in a variety of cell types, including normal and malignant colonocytes.

Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.

We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using these biomarkers, in this study we examined the anticarcinogenic mechanisms of these chemopreventive agents.

Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumor development.

Colonic tumorigenesis involves the processes of initiation and promotion/progression from normal epithelial cells to tumors. Studies in both humans and experimental models of colon cancer indicate that secondary bile acids promote tumor development. In contrast, we have demonstrated previously that another bile acid, ursodeoxycholic acid (UDCA), inhibits the development of azoxymethane (AOM)-induced colon cancer in rats.

Transforming growth factor-beta 1 signaling contributes to Caco-2 cell growth inhibition induced by 1,25(OH)(2)D(3).

Growth of Caco-2 and many cancer cells is inhibited by 1,25(OH)(2)D(3). Whereas TGF-beta 1 inhibits normal colonic epithelial cell growth, most human colon cancer-derived cells, including Caco-2 and SW480 cells, are resistant to it. The mechanisms underlying these antiproliferative actions and resistance to TGF-beta growth inhibition are largely unknown.

Regulation of rat ileal NHE3 by 1,25(OH)2-vitamin D3.

We have previously demonstrated a modulation of Na+/H+ exchange (NHE) activity by vitamin D3 in the rat ileum and Caco-2 cells. However, the molecular mechanism(s) of action of vitamin D3 on NHE are still not understood. The current studies were undertaken to understand the regulation of individual NHE isoforms on mRNA levels in two distinct models of vitamin D3 deficiency.