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World J Gastroenterol. Dec 7, 2005; 11(45): 7136-7141
Published online Dec 7, 2005. doi: 10.3748/wjg.v11.i45.7136
Upregulation of 25-hydroxyvitamin D3-1α-hydroxylase by butyrate in Caco-2 cells
Oliver Schröder, Sinan Turak, Carolin Daniel, Tanja Gaschott, Jürgen Stein
Oliver Schröder, Sinan Turak, Carolin Daniel, Tanja Gaschott, Jürgen Stein, Ist Department of Internal Medicine, Division of Gastroenterology and Clinical Nutrition, ZAFES, Johann Wolfgang Goethe-University, Frankfurt, Germany
Author contributions: All authors contributed equally to the work.
Supported by the Else Kröner-Fresenius Foundation, Bad Homburg, Germany
Correspondence to: Dr Oliver Schröder, Ist Department of Internal Medicine, Division of Gastroenterology and Clinical Nutrition, ZAFES, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. o.schroeder@em.uni-frankfurt.de
Telephone: +49-69-6301-6204 Fax: +49-69-6301-83112
Received: January 12, 2005
Revised: April 1, 2005
Accepted: April 2, 2005
Published online: December 7, 2005
Abstract

AIM: To investigate the possible involvement of 25-hydroxyvitamin D3-1α-hydroxylase [1α-25(OH)2D3] in butyrate-induced differentiation in human intestinal cell line Caco-2 cells.

METHODS: Caco-2 cells were incubated either with 3 mmol/L butyrate and 1 µmol/L 25(OH)2D3 or with 1 µmol/L 1α-25(OH)2D3 for various time intervals ranging from 0 to 72 h. Additionally, cells were co-incubated with butyrate and either 25(OH)2D3 or 1α-25(OH)2D3. 1α-25(OH)2D3 mRNA was determined semi-quantitatively using the fluorescent dye PicoGreen. Immunoblotting was used for the detection of 1α-25(OH)2D3 protein. Finally, enzymatic activity was measured by ELISA.

RESULTS: Both butyrate and 1α-25(OH)2D3 stimulated differentiation of Caco-2 cells after a 48 h incubation period, while 25(OH)2D3 had no impact on cell differentiation. Synergistic effects on differentiation were observed when cells were co-incubated with butyrate and vitamin D metabolite. Butyrate transiently upregulated 1α-25(OH)2D3 mRNA followed by a timely delayed protein upregulation. Coincidently, enzymatic activity was enhanced significantly. The induction of the enzyme allowed for comparable differentiating effects of both vitamin D metabolites.

CONCLUSION: Our experimental data provide a further mechanism for the involvement of the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate. The enhancement of 1α-25(OH)2D3 followed by antiproliferative effects of the vitamin D prohormone in the Caco-2 cell line suggest that 25(OH)2D3 in combination with butyrate may offer a new therapeutic approach for the treatment of colon cancer.

Keywords: 25-Hydroxyvitamin D3-1α-hydroxylase; Butyrate; Caco-2 cells; Colon cancer; Differentiation; Vitamin D