The Journal of Nutritional Biochemistry
Volume 21, Issue 12 , Pages 1153-1161 , December 2010

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

  • Leonid Bartik

      Affiliations

    • Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
  • ,
  • G. Kerr Whitfield

      Affiliations

    • Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
    • Department of Basic Medical Sciences, College of Medicine, The University of Arizona, Phoenix, AZ 85004, USA
  • ,
  • Magdalena Kaczmarska

      Affiliations

    • Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
  • ,
  • Christine L. Lowmiller

      Affiliations

    • Department of Nutrition, Arizona State University at the Polytechnic Campus, Mesa, AZ 85212, USA
  • ,
  • Eric W. Moffet

      Affiliations

    • School of Letters and Sciences, Arizona State University, Tempe, AZ 85287, USA
  • ,
  • Julie K. Furmick

      Affiliations

    • Division of Mathematical and Natural Sciences, Arizona State University at the West Campus, Glendale, AZ 85306, USA
  • ,
  • Zachary Hernandez

      Affiliations

    • Division of Mathematical and Natural Sciences, Arizona State University at the West Campus, Glendale, AZ 85306, USA
  • ,
  • Carol A. Haussler

      Affiliations

    • Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
    • Department of Basic Medical Sciences, College of Medicine, The University of Arizona, Phoenix, AZ 85004, USA
  • ,
  • Mark R. Haussler

      Affiliations

    • Department of Biochemistry and Molecular Biophysics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
    • Department of Basic Medical Sciences, College of Medicine, The University of Arizona, Phoenix, AZ 85004, USA
  • ,
  • Peter W. Jurutka

      Affiliations

    • Department of Basic Medical Sciences, College of Medicine, The University of Arizona, Phoenix, AZ 85004, USA
    • Division of Mathematical and Natural Sciences, Arizona State University at the West Campus, Glendale, AZ 85306, USA
    • Corresponding Author InformationCorresponding author. Division of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ 85306, USA. Tel.: +1 602 543 6087; fax: +1 602 543 6073.

Received 24 April 2009 ,Revised 11 September 2009 ,Accepted 17 September 2009.

References 

  1. Whitfield GK, Jurutka PW, Haussler CA, Hsieh JC, Barthel TK, Jacobs ET, et al. Nuclear vitamin D receptor: structure–function, molecular control of gene transcription, and novel bioactions. In:  Feldman D,  Pike JW,  Glorieux FH editor. Vitamin D. Oxford, UK: Elsevier Academic Press; 2005;p. 219–261
  2. Jurutka PW, Whitfield GK, Hsieh JC, Thompson PD, Haussler CA, Haussler MR. Molecular nature of the vitamin D receptor and its role in regulation of gene expression. Rev Endocr Metab Disord. 2001;2:203–216
  3. Haussler MR, Whitfield GK, Haussler CA, Hsieh JC, Thompson PD, Selznick SH, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res. 1998;13:325–349
  4. Holick MF. Will 1,25-dihydroxyvitamin D3, MC 903, and their analogues herald a new pharmacologic era for the treatment of psoriasis?. Arch Dermatol. 1989;125:1692–1697
  5. El-Domyati M, Barakat M, Abdel-Razek R, El-Din Anbar T. Apoptosis, P53 and Bcl-2 expression in response to topical calcipotriol therapy for psoriasis. Int J Dermatol. 2007;46:468–474
  6. Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larko O, et al. Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet. 1991;337:193–196
  7. Vijayakumar S, Mehta RR, Boerner PS, Packianathan S, Mehta RG. Clinical trials involving vitamin D analogs in prostate cancer. Cancer J. 2005;11:362–373
  8. Guyton KZ, Kensler TW, Posner GH. Vitamin D and vitamin D analogs as cancer chemopreventive agents. Nutr Rev. 2003;61:227–238
  9. Eelen G, Verlinden L, van Camp M, van Hummelen P, Marchal K, de Moor B, et al. The effects of 1alpha,25-dihydroxyvitamin D3 on the expression of DNA replication genes. J Bone Miner Res. 2004;19:133–146
  10. Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996;10:142–153
  11. Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, et al. Vitamin D receptor as an intestinal bile acid sensor. Science. 2002;296:1313–1316
  12. Nehring JA, Zierold C, DeLuca HF. Lithocholic acid can carry out in vivo functions of vitamin D. Proc Natl Acad Sci U S A. 2007;104:10006–10009
  13. Thangapazham RL, Sharma A, Maheshwari RK. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J. 2006;8:E443–E449
  14. Ruby AJ, Kuttan G, Babu KD, Rajasekharan KN, Kuttan R. Anti-tumour and antioxidant activity of natural curcuminoids. Cancer Lett. 1995;94:79–83
  15. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005;41:1955–1968
  16. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 1995;270:24995–25000
  17. Szeto FL, Sun J, Kong J, Duan Y, Liao A, Madara JL, et al. Involvement of the vitamin D receptor in the regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol. 2007;103:563–566
  18. Inoue J, Gohda J, Akiyama T, Semba K. NF-kappaB activation in development and progression of cancer. Cancer Sci. 2007;98:268–274
  19. Aggarwal BB, Banerjee S, Bharadwaj U, Sung B, Shishodia S, Sethi G. Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol. 2007;73:1024–1032
  20. Hour TC, Chen J, Huang CY, Guan JY, Lu SH, Pu YS. Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. Prostate. 2002;51:211–218
  21. Su CC, Lin JG, Li TM, Chung JG, Yang JS, Ip SW, et al. Curcumin-induced apoptosis of human colon cancer colo 205 cells through the production of ROS, Ca2+ and the activation of caspase-3. Anticancer Res. 2006;26:4379–4389
  22. Bratland A, Risberg K, Maelandsmo GM, Gutzkow KB, Olsen OE, Moghaddam A, et al. Expression of a novel factor, com1, is regulated by 1,25-dihydroxyvitamin D3 in breast cancer cells. Cancer Res. 2000;60:5578–5583
  23. Campbell MJ, Elstner E, Holden S, Uskokovic M, Koeffler HP. Inhibition of proliferation of prostate cancer cells by a 19-nor-hexafluoride vitamin D3 analogue involves the induction of p21waf1, p27kip1 and E-cadherin. J Mol Endocrinol. 1997;19:15–27
  24. Liu Y, Chang RL, Cui XX, Newmark HL, Conney AH. Synergistic effects of curcumin on all-trans retinoic acid- and 1 alpha,25-dihydroxyvitamin D3-induced differentiation in human promyelocytic leukemia HL-60 cells. Oncol Res. 1997;9:19–29
  25. Thompson PD, Jurutka PW, Whitfield GK, Myskowski SM, Eichhorst KR, Dominguez CE, et al. Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Biochem Biophys Res Commun. 2002;299:730–738
  26. Jantzen HM, Strahle U, Gloss B, Stewart F, Schmid W, Boshart M, et al. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987;49:29–38
  27. Mangelsdorf DJ, Umesono K, Kliewer SA, Borgmeyer U, Ong ES, Evans RM. A direct repeat in the cellular retinol-binding protein type II gene confers differential regulation by RXR and RAR. Cell. 1991;66:555–561
  28. Jurutka PW, Thompson PD, Whitfield GK, Eichhorst KR, Hall N, Dominguez CE, et al. Molecular and functional comparison of 1,25-dihydroxyvitamin D3 and the novel vitamin D receptor ligand, lithocholic acid, in activating transcription of cytochrome P450 3A4. J Cell Biochem. 2005;94:917–943
  29. Kingston RE. Transfection of DNA into eucaryotic cells: calcium phosphate transfection. In:  Ausubel FM,  Brent R,  Kingston RE,  Moore DD,  Siedman JG,  Smith JA, et al. editor. Current Protocols in Molecular Biology. New York: Greene Publishing and Wiley-Interscience; 1990;p. 9,1.1–9.1.4
  30. Pike JW. Monoclonal antibodies to chick intestinal receptors for 1,25-dihydroxyvitamin D3. Interaction and effects of binding on receptor function. J Biol Chem. 1984;259:1167–1173
  31. Kong J, Zhang Z, Musch MW, Ning G, Sun J, Hart J, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008;294:G208–G216
  32. Sriussadaporn S, Wong MS, Whitfield JF, Tembe V, Favus MJ. Structure-function relationship of human parathyroid hormone in the regulation of vitamin D receptor expression in osteoblast-like cells (ROS 17/2.8). Endocrinology. 1995;136:3735–3742
  33. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res. 2001;21:2895–2900
  34. Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999;27:486–494
  35. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. 1998;64:353–356
  36. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4:807–818
  37. Fang JY, Hung CF, Chiu HC, Wang JJ, Chan TF. Efficacy and irritancy of enhancers on the in-vitro and in-vivo percutaneous absorption of curcumin. J Pharm Pharmacol. 2003;55:593–601
  38. Ravindranath V, Chandrasekhara N. Absorption and tissue distribution of curcumin in rats. Toxicology. 1980;16:259–265
  39. Hoehle SI, Pfeiffer E, Solyom AM, Metzler M. Metabolism of curcuminoids in tissue slices and subcellular fractions from rat liver. J Agric Food Chem. 2006;54:756–764
  40. Shishodia S, Chaturvedi MM, Aggarwal BB. Role of curcumin in cancer therapy. Curr Probl Cancer. 2007;31:243–305
  41. Chinery R, Brockman JA, Peeler MO, Shyr Y, Beauchamp RD, Coffey RJ. Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21WAF1/CIP1 via C/EBPbeta. Nat Med. 1997;3:1233–1241
  42. Dhawan P, Peng X, Sutton AL, MacDonald PN, Croniger CM, Trautwein C, et al. Functional cooperation between CCAAT/enhancer-binding proteins and the vitamin D receptor in regulation of 25-hydroxyvitamin D3 24-hydroxylase. Mol Cell Biol. 2005;25:472–487
  43. Peng JB, Zhuang L, Berger UV, Adam RM, Williams BJ, Brown EM, et al. CaT1 expression correlates with tumor grade in prostate cancer. Biochem Biophys Res Commun. 2001;282:729–734
  44. Meyer MB, Watanuki M, Kim S, Shevde NK, Pike JW. The human transient receptor potential vanilloid type 6 distal promoter contains multiple vitamin D receptor binding sites that mediate activation by 1,25-dihydroxyvitamin D3 in intestinal cells. Mol Endocrinol. 2006;20:1447–1461
  45. Slattery ML, Sorenson AW, Ford MH. Dietary calcium intake as a mitigating factor in colon cancer. Am J Epidemiol. 1988;128:504–514
  46. Lipkin M, Newmark H. Calcium and the prevention of colon cancer. J Cell Biochem Suppl. 1995;22:65–73
  47. Guyton KZ, Kensler TW, Posner GH. Cancer chemoprevention using natural vitamin D and synthetic analogs. Annu Rev Phamacol Toxicol. 2001;41:421–442
  48. Chambeyron S, Bickmore WA. Does looping and clustering in the nucleus regulate gene expression?. Curr Opin Cell Biol. 2004;16:256–262
  49. Kim S, Yamazaki M, Zella LA, Meyer MB, Fretz JA, Shevde NK, et al. Multiple enhancer regions located at significant distances upstream of the transcriptional start site mediate RANKL gene expression in response to 1,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol. 2007;103:430–434

 This work was supported by the National Institutes of Health (Grants DK 063930 and DK 33351).

PII: S0955-2863(09)00212-5

doi: 10.1016/j.jnutbio.2009.09.012

The Journal of Nutritional Biochemistry
Volume 21, Issue 12 , Pages 1153-1161 , December 2010