Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer

Recently, it has been reported that 25-hydroxyvitarnin D3-1 alpha-hydroxylase [1 alpha(OH)ase, CYP27B1], required to convert non-toxic 25-hyxdroxyvitamin D3 [25(OH)D-3] to its active metabolite [1 alpha,25(OH)(2)D-3], is present in the epithelial cells of the human colon. In the present study, the potential chemoprotective role of 25(OH)D-3 was evaluated for colon cancer using the HT-29, human colon cancer cell line. Colon cancer cells were treated with 25(OH)D-3 (500 nM or 1 mu M), 1 alpha,25(OH)(2)D-3 (500 nM), cholecalciferol (D3, 1 mu M) or vehicle and cell number determined at days 2 and 5 post-treatment. Results showed that both 25(OH)D3 and la,25(OH)2D3 induced dose- and time-dependent antiproliferative effects on the HT-29 cells, with maximum inhibition noted at day 5. Western blot analyses revealed an up-regulation of VDR and 1 alpha(OH)ase expression following 24h of treatment with 25(OH)D3, and 1 alpha,25(OH)2D3. These results are consistent with the expression of VDR and 1 alpha(OH)ase in samples of normal colonic tissue, aberrant crypt foci (ACFs) and colon adenocarcinomas. The VDR expression was sequentially increased from normal to pre-cancerous lesions to well-differentiated tumors and then decreased in poorly differentiated tumors. Expression of I a(OH)ase was equally expressed in normal, pre-cancerous lesions and malignant human colon tissues. The increased expression of lot(OH)ase in colon cancer cells treated with the pro-hormone and its anti-proliferative effects, suggest that 25(OH)D-3 may offer possible therapeutic and chemopreventive option in colon cancer. (c) 2007 Elsevier Ltd. All rights reserved.