Chemopreventive efficacy of 25-hydroxyvitamin D3 in colon cancer.
Recently, it has been reported that 25-hydroxyvitamin D3-1alpha-hydroxylase [1alpha(OH)ase, CYP27B1], required to convert non-toxic 25-hyxdroxyvitamin D3 [25(OH)D(3)] to its active metabolite [1alpha,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) (500nM or 1muM), 1alpha,25(OH)(2)D(3) (500nM), cholecalciferol (D3, 1muM) or vehicle and cell number determined at days 2 and 5 post-treatment. Results showed that both 25(OH)D(3) and 1alpha,25(OH)(2)D(3) induced dose- and time-dependent anti-proliferative effects on the HT-29 cells, with maximum inhibition noted at day 5. Western blot analyses revealed an up-regulation of VDR and 1alpha(OH)ase expression following 24h of treatment with 25(OH)D(3), and 1alpha,25(OH)(2)D(3). These results are consistent with the expression of VDR and 1alpha(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 1alpha(OH)ase was equally expressed in normal, pre-cancerous lesions and malignant human colon tissues. The increased expression of 1alpha(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.
Murillo
Genoveva
G
Carcinogenesis and Chemoprevention Division, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616, USA.
Matusiak
Damien
D
Benya
Richard V
RV
Mehta
Rajendra G
RG
D002112:Calcifediol / Q000494:pharmacology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism
D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; D002112:Calcifediol