Curcumin: A novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention

Leonid Bartik, G Kerr Whitfield, Magdalena Kaczmarska, Christine L. Lowmiller, Eric W. Moffet, Julie K. Furmick, Zachary Hernandez, Carol A. Haussler, Mark R Haussler, Peter W. Jurutka

Research output: Contribution to journalArticle

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Abstract

The nuclear vitamin D receptor (VDR) mediates the actions of 1,25-dihydroxyvitamin D3 (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.

Original languageEnglish (US)
Pages (from-to)1153-1161
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume21
Issue number12
DOIs
StatePublished - Dec 2010

Fingerprint

Calcitriol Receptors
Curcumin
Chemoprevention
Colonic Neoplasms
Ligands
Calcitriol
Caco-2 Cells
Transcription
Genes
Retinoid X Receptors
Cytochrome P-450 CYP3A
Chemical activation
Real-Time Polymerase Chain Reaction
Assays
Nuclear Receptor Coactivator 1
Lithocholic Acid
Intestinal Neoplasms
Curcuma
Detoxification
Two-Hybrid System Techniques

Keywords

  • Anticancer diet
  • Cancer prevention
  • Curcumin
  • Retinoid X receptor
  • Turmeric
  • Vitamin D receptor

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Curcumin : A novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. / Bartik, Leonid; Whitfield, G Kerr; Kaczmarska, Magdalena; Lowmiller, Christine L.; Moffet, Eric W.; Furmick, Julie K.; Hernandez, Zachary; Haussler, Carol A.; Haussler, Mark R; Jurutka, Peter W.

In: Journal of Nutritional Biochemistry, Vol. 21, No. 12, 12.2010, p. 1153-1161.

Research output: Contribution to journalArticle

Bartik, Leonid ; Whitfield, G Kerr ; Kaczmarska, Magdalena ; Lowmiller, Christine L. ; Moffet, Eric W. ; Furmick, Julie K. ; Hernandez, Zachary ; Haussler, Carol A. ; Haussler, Mark R ; Jurutka, Peter W. / Curcumin : A novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention. In: Journal of Nutritional Biochemistry. 2010 ; Vol. 21, No. 12. pp. 1153-1161.
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