Butyrate-induced differentiation of Caco-2 cells is mediated by vitamin D receptor.
Butyrate in combination with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] produces a synergistic effect on cell differentiation of human colon cancer cells (Caco-2). The objective of this study was to confirm the role of the vitamin D receptor (VDR) in butyrate-induced cell differentiation of Caco-2. We studied the effects of the novel VDR antagonist ZK 191732 on butyrate-induced cell differentiation and on p21Waf1/Cip1 expression. Butyrate induced cell differentiation which was further enhanced after addition of 1,25-(OH)2D3. Experiments using ZK 191732 indicate that the synergistic effect of butyrate and 1,25-(OH)2D3 was due to butyrate-induced upregulation of VDR. While butyrate alone increased expression of p21Waf1/Cip1 and combined exposure of butyrate and 1,25-(OH)2D3 resulted in a synergistic amplification, p21Waf1/Cip1 expression did not change from the control level after treatment with butyrate plus ZK 191732. These data further imply that butyrate-induced differentiation and p21Waf1/Cip1 expression of Caco-2 cells occur via upregulation of VDR.
Gaschott
T
T
Second Department of Medicine, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
Werz
O
O
Steinmeyer
A
A
Steinhilber
D
D
Stein
J
J
D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018167:Receptors, Calcitriol / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D002087:Butyrates; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018167:Receptors, Calcitriol; D013844:Thiazoles; C440893:ZK 191732