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.
Bartik L1, Whitfield GK, Kaczmarska M, Lowmiller CL, Moffet EW, Furmick JK, Hernandez Z, Haussler CA, Haussler MR, Jurutka PW.
Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
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.
PMID: 20153625 PMCID: PMC2891903 DOI: 10.1016/j.jnutbio.2009.09.012
Clipped from PDF: 8 grams of Curcumin
- “Activation of VDR by CM required a much higher concentration (10−6 to 10−5 M) than the endocrine 1,25D ligand (10−8M), suggesting that a relatively low-affinity ligand may not achieve physiologic levels. However, up to 8 g of CM can be safely administered orally to human subjects on a daily basis, potentially leading to plasma concentrations greater than 10−6M ”
The only time I have ever been in a hospital was due to a kidney stone. was this year at age 71
2 weeks before the hospital visit I had started taking some highly-bioavailable Curcumin
When I got home later that morning I Googled "Kidney stones" curcumin I got 200,000 hits
Curcumin has a lot of oxalates, which " bind to calcium, and form insoluble calcium oxalate, which is responsible for approximately three-quarters of all kidney stones"
I now use standard-strength curcumin daily, with no problems
By the way, I got rid of my small kidney stone by using a vibrator