Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention.
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Bartik L, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, Hernandez Z, Haussler CA, Haussler MR, Jurutka PW
Curcumin: a novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention.
J Nutr Biochem. 2010 Dec;21(12):1153-61. doi: 10.1016/j.jnutbio.2009.09.012. Epub 2010 Feb 12.
- PubMed ID
- 20153625 [ View in PubMed]
- Abstract
The nuclear vitamin D receptor (VDR) mediates the actions of 1,25-dihydroxyvitamin D(3) (1,25D) to regulate gene transcription. Recently, the secondary bile acid, lithocholate (LCA), was recognized as a novel VDR ligand. Using reporter gene and mammalian two-hybrid systems, immunoblotting, competitive ligand displacement and quantitative real-time PCR, we identified curcumin (CM), a turmeric-derived bioactive polyphenol, as a likely additional novel ligand for VDR. CM (10(-5) M) activated transcription of a luciferase plasmid containing the distal vitamin D responsive element (VDRE) from the human CYP3A4 gene at levels comparable to 1,25D (10(-8) M) in transfected human colon cancer cells (Caco-2). While CM also activated transcription via a retinoid X receptor (RXR) responsive element, activation of the glucocorticoid receptor (GR) by CM was negligible. Competition binding assays with radiolabeled 1,25D confirmed that CM binds directly to VDR. In mammalian two-hybrid assays employing transfected Caco-2 cells, CM (10(-5) M) increased the ability of VDR to recruit its heterodimeric partner, RXR, and steroid receptor coactivator-1 (SRC-1). Real-time PCR studies revealed that CM-bound VDR can activate VDR target genes CYP3A4, CYP24, p21 and TRPV6 in Caco-2 cells. Numerous studies have shown chemoprotection by CM against intestinal cancers via a variety of mechanisms. Small intestine and colon are important VDR-expressing tissues where 1,25D has known anticancer properties that may, in part, be elicited by activation of CYP-mediated xenobiotic detoxification and/or up-regulation of the tumor suppressor p21. Our results suggest the novel hypothesis that nutritionally-derived CM facilitates chemoprevention via direct binding to, and activation of, VDR.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Curcumin Vitamin D3 receptor Protein Humans UnknownNot Available Details Curcumin sulfate Vitamin D3 receptor Protein Humans UnknownNot Available Details - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Curcumin Approved Investigational CDKN1A 1026 upregulated [Curcumin binds to and results in increased activity of VDR protein] which results in increased expression of CDKN1A mRNA 6p21.2 Curcumin Approved Investigational CYP24A1 1591 upregulated [Curcumin binds to and results in increased activity of VDR protein] which results in increased expression of CYP24A1 mRNA 20q13.2 Curcumin Approved Investigational CYP3A4 1576 upregulated [Curcumin binds to and results in increased activity of VDR protein] which results in increased expression of CYP3A4 mRNA 7q22.1 Curcumin Approved Investigational TRPV6 55503 upregulated [Curcumin binds to and results in increased activity of VDR protein] which results in increased expression of TRPV6 mRNA 7q34 Calcitriol Approved Nutraceutical VDR 7421 upregulated Calcitriol results in increased expression of VDR mRNA 12q13.11 - Pharmaco-proteomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Calcitriol Approved Nutraceutical VDR 7421 increased Calcitriol results in increased expression of VDR protein 12q13.11