Therapeutic targets of vitamin D receptor ligands and their pharmacokinetic effects by modulation of transporters and metabolic enzymes

  • Min Sik Choi
  • Yu Chul KimEmail author
  • Han-Joo MaengEmail author


Vitamin D is involved in retaining the balance of several minerals in the body, such as calcium and phosphate, which are crucial for the bone formation and development. These physiological effects of vitamin D are mediated by activation of the transcription factor vitamin D receptor (VDR). Moreover, vitamin D is closely related to several pathological conditions including osteoporosis, secondary hyperparathyroidism, cancer, psoriasis and autoimmune diseases, which is not only due to calcemic but also non-calcemic effects of vitamin D such as cell proliferation, differentiation, and immunomodulation. These various abilities of vitamin D have made VDR an attractive therapeutic target. Already, numerous vitamin D analogs have been developed and studied in in vitro disease models or animal models, and some have been in clinical trials or approved for the treatment of certain diseases. In addition, the transcriptional and/or post-transcriptional regulation by VDR activation also affects the genes involved in drug metabolism and disposition, possibly leading to pharmacokinetic changes of several drugs in clinical use. This review provides a detailed summary of therapeutic targets of VDR ligands, and their effects on the transporters and metabolic enzymes, causing in vitro and in vivo pharmacokinetic changes of several drugs. The clinical research is further required for the confirming the clinical relevance of pharmacokinetic drug interactions by VDR ligands.


Vitamin D Vitamin D receptor (VDR) Therapeutic target Transporters Metabolic enzymes Pharmacokinetics 



This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1D1A1B03931470).

Compliance with ethical standards

Conflict of the interest

These authors declare that they have no conflict of interest.

Human and animal rights participants

All institutional and national guidelines for the care and use of laboratory animals were followed.


  1. Abou-Raya A, Abou-Raya S, Helmii M (2013) The effect of vitamin D supplementation on inflammatory and hemostatic markers and disease activity in patients with systemic lupus erythematosus: a randomized placebo-controlled trial. J Rheumatol 40:265–272CrossRefPubMedGoogle Scholar
  2. Adami S, Giannini S, Bianchi G, Sinigaglia L, Di Munno O, Fiore CE, Minisola S, Rossini M (2009) Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos Int 20:239–244CrossRefPubMedGoogle Scholar
  3. Aguilera O, Peña C, García JM, Larriba MJ, Ordóñez-Morán P, Navarro D, Barbáchano A, López de Silanes I, Ballestar E, Fraga MF, Esteller M, Gamallo C, Bonilla F, González-Sancho JM, Muñoz A (2007) The Wnt antagonist DICKKOPF-1 gene is induced by 1α,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis 28:1877–1884CrossRefPubMedGoogle Scholar
  4. Åivo J, Hänninen A, Ilonen J, Soilu-Hänninen M (2015) Vitamin D3 administration to MS patients leads to increased serum levels of latency activated peptide (LAP) of TGF-beta. J Neuroimmunol 280:12–15CrossRefPubMedGoogle Scholar
  5. Akizawa T, Suzuki M, Akiba T, Nishizawa Y, Ohashi Y, Ogata E, Slatopolsky E, Kurokawa K (2002) Long-term effect of 1,25-dihydroxy-22-oxavitamin D(3) on secondary hyperparathyroidism in haemodialysis patients. One-year administration study. Nephrol Dial Transplant 17(Suppl. 10):28–36CrossRefPubMedGoogle Scholar
  6. Akizawa T, Ohashi Y, Akiba T, Suzuki M, Nishizawa Y, Ogata E, Slatopolsky E, Kurokawa K (2004) Dose-response study of 22-oxacalcitriol in patients with secondary hyperparathyroidism. Ther Apher Dial 8:480–491CrossRefPubMedGoogle Scholar
  7. Albert DM, Kumar A, Strugnell SA, Darjatmoko SR, Lokken JM, Lindstrom MJ, Patel S (2004) Effectiveness of vitamin D analogues in treating large tumors and during prolonged use in murine retinoblastoma models. Arch Ophthalmol 122:1357–1362CrossRefPubMedGoogle Scholar
  8. Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS, Chan AT (2012) Higher predicted vitamin D status is associated with reduced risk of Crohn’s disease. Gastroenterology 142:482–489CrossRefPubMedGoogle Scholar
  9. Barker JN, Ashton RE, Marks R, Harris RI, Berth-Jones J (1999) Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-finding study with active comparator. Br J Dermatol 141:274–278CrossRefPubMedGoogle Scholar
  10. Barrett KG, Fang H, Kocarek TA, Runge-Morris M (2016) Transcriptional regulation of cytosolic sulfotransferase 1C2 by vitamin D receptor in LS180 human colorectal adenocarcinoma cells. Drug Metab Dispos 44(8):1431–1434CrossRefPubMedPubMedCentralGoogle Scholar
  11. Beer TM, Myrthue A (2004) Calcitriol in cancer treatment: from the lab to the clinic. Mol Cancer Ther 3:373–381PubMedGoogle Scholar
  12. Bell TD, Demay MB, Burnett-Bowie SA (2010) The biology and pathology of vitamin D control in bone. J Cell Biochem 111:7–13CrossRefPubMedPubMedCentralGoogle Scholar
  13. Bener A, Ehlayel MS, Tulic MK, Hamid Q (2012) Vitamin D deficiency as a strong predictor of asthma in children. Int Arch Allergy Immunol 157:168–175CrossRefPubMedGoogle Scholar
  14. Bernardi RJ, Johnson CS, Modzelewski RA, Trump DL (2002) Antiproliferative effects of 1α,25-dihydroxyvitamin D(3) and vitamin D analogs on tumor-derived endothelial cells. Endocrinology 143:2508–2514CrossRefPubMedGoogle Scholar
  15. Bhatia V, Saini MK, Shen X, Bi LX, Qiu S, Weigel NL, Falzon M (2009) EB1089 inhibits the parathyroid hormone-related protein-enhanced bone metastasis and xenograft growth of human prostate cancer cells. Mol Cancer Ther 8:1787–1798CrossRefPubMedPubMedCentralGoogle Scholar
  16. Bikle DD (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319–329CrossRefPubMedPubMedCentralGoogle Scholar
  17. Bikle DD, Chang S, Crumrine D, Elalieh H, Man MQ, Choi EH, Dardenne O, Xie Z, Arnaud RS, Feingold K, Elias PM (2004) 25-Hydroxyvitamin D 1 α-hydroxylase is required for optimal epidermal differentiation and permeability barrier homeostasis. J Invest Dermatol 122:984–992CrossRefPubMedGoogle Scholar
  18. Bollag WB (2007) Differentiation of human keratinocytes requires the Vitamin D receptor and its coactivators. J Invest Dermatol 127:748–750CrossRefPubMedGoogle Scholar
  19. Bricker NS (1972) On the pathogenesis of the uremic state. An exposition of the ‘trade-off hypothesis’. N Engl J Med 286:1093–1099CrossRefPubMedGoogle Scholar
  20. Brown AJ, Ritter CR, Finch JL, Morrissey J, Martin KJ, Murayama E, Nishii Y, Slatopolsky E (1989) The noncalcemic analogue of vitamin D, 22-oxacalcitriol, suppresses parathyroid hormone synthesis and secretion. J Clin Invest 84:728–732CrossRefPubMedPubMedCentralGoogle Scholar
  21. Brown AJ, Finch JL, Lopez-Hilker S, Dusso A, Ritter C, Pernalete N, Slatopolsky E (1990) New active analogues of vitamin D with low calcemic activity. Kidney Int 29(Suppl. 29):S22–S27Google Scholar
  22. Campbell MJ, Koeffler HP (1997) Toward therapeutic intervention of cancer by vitamin D compounds. J Natl Cancer Inst 89:182–185CrossRefPubMedGoogle Scholar
  23. Carlberg C (1995) Mechanisms of nuclear signalling by vitamin D3. Interplay with retinoid and thyroid hormone signalling. Eur J Biochem 231(3):517–527CrossRefPubMedGoogle Scholar
  24. Chen X, Chen F, Liu S, Glaeser H, Dawson PA, Hofmann AF, Kim RB, Shneider BL, Pang KS (2006) Transactivation of rat apical sodium-dependent bile acid transporter and increased bile acid transport by 1α,25-dihydroxyvitamin D3 via the vitamin D receptor. Mol Pharmacol 69:1913–1923CrossRefPubMedGoogle Scholar
  25. Cheng J, Fang ZZ, Kim JH, Krausz KW, Tanaka N, Chiang JY, Gonzalez FJ (2014) Intestinal CYP3A4 protects against lithocholic acid-induced hepatotoxicity in intestine-specific VDR-deficient mice. J Lipid Res 55(3):455–465CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chiang KC, Yeh CN, Hsu JT, Yeh TS, Jan YY, Wu CT, Chen HY, Jwo SC, Takano M, Kittaka A, Juang HH, Chen TC (2013) Evaluation of the potential therapeutic role of a new generation of vitamin D analog, MART-10, in human pancreatic cancer cells in vitro and in vivo. Cell Cycle 15:1316–1325CrossRefGoogle Scholar
  27. Chow EC, Durk MR, Maeng HJ, Pang KS (2009) 1α,25-Dihydroxyvitamin D(3) triggered vitamin D receptor and farnesoid X receptor-like effects in rat intestine and liver in vivo. Biopharm Drug Dispos 30:457–475CrossRefPubMedGoogle Scholar
  28. Chow EC, Sun H, Khan AA, Groothuis GM, Pang KS (2010) Effects of 1α,25-dihydroxyvitamin D3 on transporters and enzymes of the rat intestine and kidney in vivo.. Biopharm Drug Dispos 31:91–108PubMedGoogle Scholar
  29. Chow EC, Durk MR, Cummins CL, Pang KS (2011a) 1A,25-dihydroxyvitamin D3 up-regulates P-glycoprotein via the vitamin D receptor and not farnesoid X receptor in both fxr(-/-) and fxr(+/+) mice and increased renal and brain efflux of digoxin in mice in vivo. J Pharmacol Exp Ther 337:846–859CrossRefPubMedGoogle Scholar
  30. Chow EC, Sondervan M, Jin C, Groothuis GM, Pang KS (2011b) Comparative effects of doxercalciferol (1α-hydroxyvitamin D2) versus calcitriol (1α,25-dihydroxyvitamin D3) on the expression of transporters and enzymes in the rat in vivo. J Pharm Sci 100:1594–1604CrossRefPubMedGoogle Scholar
  31. Chow EC, Durk MR, Maeng HJ, Pang KS (2013) Comparative effects of 1α-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on transporters and enzymes in fxr(+/+) and fxr(-/-) mice. Biopharm Drug Dispos 34:402–416PubMedGoogle Scholar
  32. Chung I, Han G, Seshadri M, Gillard BM, Yu WD, Foster BA, Trump DL, Johnson CS (2009) Role of vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Res 69:967–975CrossRefPubMedPubMedCentralGoogle Scholar
  33. Coburn JW, Maung HM, Elangovan L, Germain MJ, Lindberg JS, Sprague SM, Williams ME, Bishop CW (2004) Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Am J Kidney Dis 43(5):877–890CrossRefPubMedGoogle Scholar
  34. Colston K, Colston MJ, Feldman D (1981) 1,25-Dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology 108:1083–1086CrossRefPubMedGoogle Scholar
  35. Colston KW, Chander SK, Mackay AG, Coombes RC (1992) Effects of synthetic vitamin D analogues on breast cancer cell proliferation in vivo and in vitro. Biochem Pharmacol 44:693–702CrossRefPubMedGoogle Scholar
  36. Colston KW, James SY, Ofori-Kuragu EA, Binderup L, Grant AG (1997) Vitamin D receptors and anti-proliferative effects of vitamin D derivatives in human pancreatic carcinoma cells in vivo and in vitro. Br J Cancer 76:1017–1020CrossRefPubMedPubMedCentralGoogle Scholar
  37. Cross HS, Huber C, Peterlik M (1991) Antiproliferative effect of 1,25-dihydroxyvitamin D3 and its analogs on human colon adenocarcinoma cells (CaCo-2): influence of extracellular calcium. Biochem Biophys Res Commun 179:57–62CrossRefPubMedGoogle Scholar
  38. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM (2008) Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. Pharmacol Exp Ther 324:23–33CrossRefGoogle Scholar
  39. DeLuca HF (2008) Evolution of our understanding of vitamin D. Nutr Rev 66:S73–S87CrossRefPubMedGoogle Scholar
  40. DeLuca HF, Bedale W, Binkley N, Gallagher JC, Bolognese M, Peacock M, Aloia J, Clagett-Dame M, Plum L (2011) The vitamin D analogue 2MD increases bone turnover but not BMD in postmenopausal women with osteopenia: results of a 1-year phase 2 double-blind, placebo-controlled, randomized clinical trial. J Bone Miner Res 26:538–545CrossRefPubMedGoogle Scholar
  41. Di Filippo P, Scaparrotta A, Rapino D, Cingolani A, Attanasi M, Petrosino MI, Chuang K, Di Pillo S, Chiarelli F (2015) Vitamin D supplementation modulates the immune system and improves atopic dermatitis in children. Int Arch Allergy Immunol 166:91–96CrossRefPubMedGoogle Scholar
  42. Drocourt L, Ourlin JC, Pascussi JM, Maurel P, Vilarem MJ (2002) Expression of CYP3A4, CYP2B6, and CYP2C9 is regulated by the vitamin D receptor pathway in primary human hepatocytes. J Biol Chem 277(28):25125–25132CrossRefPubMedGoogle Scholar
  43. Durakovic C, Malabanan A, Holick MF (2001) Rationale for use and clinical responsiveness of hexafluoro-1,25-dihydroxyvitamin D3 for the treatment of plaque psoriasis: a pilot study. Br J Dermatol 144:500–506CrossRefPubMedGoogle Scholar
  44. Duranton F, Rodriguez-Ortiz ME, Duny Y, Rodriguez M, Daurès JP, Argilés A (2013) Vitamin D treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am J Nephrol 37:239–248CrossRefPubMedGoogle Scholar
  45. Echchgadda I, Song CS, Roy AK, Chatterjee B (2004) Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor. Mol Pharmacol 65(3):720–729CrossRefPubMedGoogle Scholar
  46. El-Agroudy AE, El-Husseini AA, El-Sayed M, Ghoneim MA (2003) Preventing bone loss in renal transplant recipients with vitamin D. J Am Soc Nephrol 14:2975–2979CrossRefPubMedGoogle Scholar
  47. Eloranta JJ, Hiller C, Jüttner M, Kullak-Ublick GA (2012) The SLCO1A2 gene, encoding human organic anion-transporting polypeptide 1A2, is transactivated by the vitamin D receptor. Mol Pharmacol 82:37–46CrossRefPubMedGoogle Scholar
  48. Fan J, Liu S, Du Y, Morrison J, Shipman R, Pang KS (2009) Up-regulation of transporters and enzymes by the vitamin D receptor ligands, 1α,25-dihydroxyvitamin D3 and vitamin D analogs, in the Caco-2 cell monolayer. J Pharmacol Exp Ther 330:389–402CrossRefPubMedGoogle Scholar
  49. Felsenberg D, Bock O, Borst H, Armbrecht G, Beller G, Degner C, Stephan-Oelkers M, Schacht E, Mazor Z, Hashimoto J, Roth HJ, Martus P, Runge M (2011) Additive impact of alfacalcidol on bone mineral density and bone strength in alendronate treated postmenopausal women with reduced bone mass. J Musculoskelet Neuronal Interact 11:34–45PubMedGoogle Scholar
  50. Francis RM, Boyle IT, Moniz C, Sutcliffe AM, Davis BS, Beastall GH, Cowan RA, Downes N (1996) A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures. Osteoporos Int 6:284–290CrossRefPubMedGoogle Scholar
  51. Fujioka T, Hasegawa M, Ishikura K, Matsushita Y, Sato M, Tanji S (1998) Inhibition of tumor growth and angiogenesis by vitamin D3 agents in murine renal cell carcinoma. J Urol 160:247–251CrossRefPubMedGoogle Scholar
  52. Fujita T, Orimo H, Inoue T, Kaneda K, Sakurai M, Morita R, Yamamoto K, Sugioka Y, Inoue A, Takaoka K, Yamamoto I, Hoshino Y, Kawaguchi H (2007) Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol. J Bone Miner Metab 25:130–137CrossRefPubMedGoogle Scholar
  53. Getzenberg RH, Light BW, Lapco PE, Konety BR, Nangia AK, Acierno JS, Dhir R, Shurin Z, Day RS, Trump DL, Johnson CS (1997) Vitamin D inhibition of prostate adenocarcinoma growth and metastasis in the Dunning rat prostate model system. Urology 50:999–1006CrossRefPubMedGoogle Scholar
  54. Ghous Z, Akhter J, Pourgholami MH, Morris DL (2008) Inhibition of hepatocellular cancer by EB1089: in vitro and in vivo study. Anticancer Res 28:3757–3761PubMedGoogle Scholar
  55. Goto S, Komaba H, Fukagawa M (2008) Pathophysiology of parathyroid hyperplasia in chronic kidney disease: preclinical and clinical basis for parathyroid intervention. NDT Plus 1(Suppl 3):iii2–iii8PubMedPubMedCentralGoogle Scholar
  56. Grostern RJ, Bryar PJ, Zimbric ML, Darjatmoko SR, Lissauer BJ, Lindstrom MJ, Lokken JM, Strugnell SA, Albert DM (2002) Toxicity and dose-response studies of 1α-hydroxyvitamin D2 in a retinoblastoma xenograft model. Arch Ophthalmol 120:607–612CrossRefPubMedGoogle Scholar
  57. Guo X, Meng Q, Liu Q, Wang C, Mao Q, Sun H, Peng J, Kaku T, Liu K (2012) Peptide cotransporter 1 in intestine and organic anion transporters in kidney are targets of interaction between JBP485 and lisinopril in rats. Drug Metab Pharmacokinet 27:232–241CrossRefPubMedGoogle Scholar
  58. Guzey M, Kitada S, Reed JC (2002) Apoptosis induction by 1α,25-dihydroxyvitamin D3 in prostate cancer. Mol Cancer Ther 1:667–677PubMedGoogle Scholar
  59. Hara K, Kusuzaki K, Takeshita H, Kuzuhara A, Tsuji Y, Ashihara T, Hirasawa Y (2001) Oral administration of 1α hydroxyvitamin D3 inhibits tumor growth and metastasis of a murine osteosarcoma model. Anticancer Res 21:321–324PubMedGoogle Scholar
  60. Hargrove L, Francis T, Francis H (2014) Vitamin D and GI cancers: shedding some light on dark diseases. Ann Transl Med 2:9PubMedPubMedCentralGoogle Scholar
  61. Hayashi M, Tsuchiya Y, Itaya Y, Takenaka T, Kobayashi K, Yoshizawa M, Nakamura R, Monkawa T, Ichihara A (2004) Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial. Nephrol Dial Transplant 19:2067–2073CrossRefPubMedGoogle Scholar
  62. Hirata M, Endo K, Katsumata K, Ichikawa F, Kubodera N, Fukagawa M (2002) A comparison between 1,25-dihydroxy-22-oxavitamin D3 and 1,25-dihydroxyvitamin D3 regarding suppression of parathyroid hormone and calcemic action. Nephrol Dial Transplant 17(suppl 10):41–45CrossRefPubMedGoogle Scholar
  63. Holick MF (2004) Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 79:362–371CrossRefPubMedGoogle Scholar
  64. Holick MF, Chen ML, Kong XF, Sanan DK (1996) Clinical uses for calciotropic hormones 1,25-dihydroxyvitamin D3 and parathyroid hormone-related peptide in dermatology: a new perspective. J Investig Dermatol Symp Proc 1:1–9PubMedGoogle Scholar
  65. Imanishi Y, Inaba M, Seki H, Koyama H, Nishizawa Y, Morii H, Otani S (1999) Increased biological potency of hexafluorinated analogs of 1,25-dihydroxyvitamin D3 on bovine parathyroid cells. J Steroid Biochem Mol Biol 70:243–248CrossRefPubMedGoogle Scholar
  66. Jiang F, Li P, Fornace AJ Jr, Nicosia SV, Bai W (2003) G2/M arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer. J Biol Chem 278:48030–48040CrossRefPubMedGoogle Scholar
  67. Katayama I, Ohkawara A, Ohkido M, Harada S, Tamaki K, Nakagawa H, Hori Y, Nishiyama S (2002) High-concentration (20 mug/g) tacalcitol ointment therapy on refractory psoriasis vulgaris with low response to topical corticosteroids. Eur J Dermatol 12:553–557PubMedGoogle Scholar
  68. Kawa S, Yoshizawa K, Tokoo M, Imai H, Oguchi H, Kiyosawa K, Homma T, Nikaido T, Furihata K (1996) Inhibitory effect of 220-oxa-1,25-dihydroxyvitamin D3 on the proliferation of pancreatic cancer cell lines. Gastroenterology 110:1605–1613CrossRefPubMedGoogle Scholar
  69. Ke HZ, Qi H, Crawford DT, Simmons HA, Xu G, Li M, Plum L, Clagett-Dame M, DeLuca HF, Thompson DD, Brown TA (2005) A new vitamin D analog, 2MD, restores trabecular and cortical bone mass and strength in ovariectomized rats with established osteopenia. J Bone Miner Res 20:1742–1755CrossRefPubMedGoogle Scholar
  70. Khan AA, Chow EC, van Loenen-Weemaes AM, Porte RJ, Pang KS, Groothuis GM (2009) Comparison of effects of VDR versus PXR, FXR and GR ligands on the regulation of CYP3A isozymes in rat and human intestine and liver. Eur J Pharm Sci 37(2):115–125CrossRefPubMedGoogle Scholar
  71. Kim YC, Kim IB, Noh CK, Quach HP, Yoon IS, Chow ECY, Kim M, Jin HE, Cho KH, Chung SJ, Pang KS, Maeng HJ (2014) Effects of 1α,25-dihydroxyvitamin D3, the natural vitamin D receptor ligand, on the pharmacokinetics of cefdinir and cefadroxil, organic anion transporter substrates, in rat. J Pharm Sci 103:3793–3805CrossRefPubMedGoogle Scholar
  72. Kota BP, Abdul MI, Allen JD, Kalagara M, Roufogalis BD (2012) Effect of vitamin D3 supplementation on the pharmacokinetics of digoxin—a pilot study. Fundam Clin Pharmacol 26:543–548CrossRefPubMedGoogle Scholar
  73. Kragballe K, Beck HI, Søgaard H (1988) Improvement of psoriasis by a topical vitamin D3 analogue (MC 903) in a double-blind study. Br J Dermatol 119:223–230CrossRefPubMedGoogle Scholar
  74. Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larkö O, Nieboer C, Roed-Petersen J, Strand A, Tikjøb G (1991) Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 337:193–196CrossRefPubMedGoogle Scholar
  75. Kubodera N, Tsuji N, Uchiyama Y, Endo K (2003) A new active vitamin D analog, ED-71, causes increase in bone mass with preferential effects on bone in osteoporotic patients. J Cell Biochem 88:286–289CrossRefPubMedGoogle Scholar
  76. Kumagai T, O’Kelly J, Said JW, Koeffler HP (2003) Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. J Natl Cancer Inst 95:896–905CrossRefPubMedGoogle Scholar
  77. LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowacki J (1999) Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 251:1505–1511CrossRefGoogle Scholar
  78. Lee HJ, So JY, DeCastro A, Smolarek A, Paul S, Maehr H, Uskokovic M, Suh N (2010) Gemini vitamin D analog suppresses ErbB2-positive mammary tumor growth via inhibition of ErbB2/AKT/ERK signaling. J Steroid Biochem Mol Biol 121:408–412CrossRefPubMedPubMedCentralGoogle Scholar
  79. Lehmann B, Querings K, Reichrath J (2004) Vitamin D and skin: new aspects for dermatology. Exp Dermatol 13 Suppl 4:11–15CrossRefGoogle Scholar
  80. Lemire J (2000) 1,25-Dihydroxyvitamin D3-a hormone with immunomodulatory properties. Z Rheumatol 59(Suppl 1):24–27CrossRefPubMedGoogle Scholar
  81. Levin AD, Wadhera V, Leach ST, Woodhead HJ, Lemberg DA, Mendoza-Cruz AC, Day AS (2011) Vitamin D deficiency in children with inflammatory bowel disease. Dig Dis Sci 56:830–836CrossRefPubMedGoogle Scholar
  82. Leyssens C, Verlinden L, Verstuyf A (2014) The future of vitamin D analogs. Front Physiol 5:122CrossRefPubMedPubMedCentralGoogle Scholar
  83. Li P, Li C, Zhao X, Zhang X, Nicosia SV, Bai W (2004) p27(Kip1) stabilization and G(1) arrest by 1,25-dihydroxyvitamin D(3) in ovarian cancer cells mediated through down-regulation of cyclin E/cyclin-dependent kinase 2 and Skp1-Cullin-F-box protein/Skp2 ubiquitin ligase. J Biol Chem 279:25260–25267CrossRefPubMedGoogle Scholar
  84. Li F, Peng M, Jiang L, Sun Q, Zhang K, Lian F, Litonjua AA, Gao J, Gao X (2011) Vitamin D deficiency is associated with decreased lung function in Chinese adults with asthma. Respiration 81:469–475CrossRefPubMedGoogle Scholar
  85. Ma Y, Yu WD, Trump DL, Johnson CS (2010) 1,25D3 enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models. Cancer 116:3294–3303CrossRefPubMedPubMedCentralGoogle Scholar
  86. Ma Y, Yu WD, Hidalgo AA, Luo W, Delansorne R, Johnson CS, Trump DL (2013) Inecalcitol, an analog of 1,25D3, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system. Cell Cycle 12:743–752CrossRefPubMedPubMedCentralGoogle Scholar
  87. Maeng HJ, Durk MR, Chow EC, Ghoneim R, Pang KS (2011) 1α,25-dihydroxyvitamin D3 on intestinal transporter function: studies with the rat everted intestinal sac. Biopharm Drug Dispos 32:112–125CrossRefPubMedGoogle Scholar
  88. Maeng HJ, Chapy H, Zaman S, Pang KS (2012) Effects of 1α,25-dihydroxyvitamin D3 on transport and metabolism of adefovir dipivoxil and its metabolites in Caco-2 cells. Eur J Pharm Sci 46:149–166CrossRefPubMedGoogle Scholar
  89. Majewski S, Skopinska M, Marczak M, Szmurlo A, Bollag W, Jablonska S (1996) Vitamin D3 is a potent inhibitor of tumor cell-induced angiogenesis. J Investig Dermatol Symp Proc 1:97–101PubMedGoogle Scholar
  90. Makishima M, Lu TT, Xie W, Whitfield GK, Domoto H, Evans RM, Haussler MR, Mangelsdorf DJ (2002) Vitamin D receptor as an intestinal bile acid sensor. Science 17:1313–1316CrossRefGoogle Scholar
  91. Mantell DJ, Owens PE, Bundred NJ, Mawer EB, Canfield AE (2000) 1 α,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo. Circ Res 87:214–220CrossRefPubMedGoogle Scholar
  92. Marchwicka A, Cebrat M, Sampath P, Snieżewski L, Marcinkowska E (2014) Perspectives of differentiation therapies of acute myeloid leukemia: the search for the molecular basis of patients’ variable responses to 1,25-dihydroxyvitamin d and vitamin d analogs. Front Oncol 4:125CrossRefPubMedPubMedCentralGoogle Scholar
  93. Martin KJ, Gonzales EA, Gellens M, Hamm LL, Abboud H, Lindberg J (1998a) 19-Nor-1a,25-dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol 9:1427–1432PubMedGoogle Scholar
  94. Martin KJ, Gonzalez EA, Gellens ME, Hamm LL, Abboud H, Lindberg J (1998b) Therapy of secondary hyperparathyroidism with 19-nor-1a,25-dihydroxyvitamin D2. Am J Kidney Dis 32:S61–S66CrossRefPubMedGoogle Scholar
  95. Martinelli V, Dalla Costa G, Colombo B, Dalla Libera D, Rubinacci A, Filippi M, Furlan R, Comi G (2014) Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes. Mult Scler 20:147–155CrossRefPubMedGoogle Scholar
  96. McCarthy TC, Li X, Sinal CJ (2005) Vitamin D receptor-dependent regulation of colon multidrug resistance-associated protein 3 gene expression by bile acids. J Biol Chem 280(24):23232–23242CrossRefPubMedGoogle Scholar
  97. McGuire TF, Trump DL, Johnson CS (2001) Vitamin D(3)-induced apoptosis of murine squamous cell carcinoma cells. Selective induction of caspase-dependent MEK cleavage and up-regulation of MEKK-1. J Biol Chem 276:26365–26373CrossRefPubMedGoogle Scholar
  98. Meyer MB, Goetsch PD, Pike JW (2012) VDR/RXR and TCF4/beta-catenin cistromes in colonic cells of colorectal tumor origin: impact on c-FOS and c-MYC gene expression. Mol Endocrinol 26:37–51CrossRefPubMedGoogle Scholar
  99. Miao Q, Liu Q, Wang C, Meng Q, Guo X, Sun H, Peng J, Ma X, Kaku T, Liu K (2013) Inhibitory effect of 1α,25-dihydroxyvitamin D3 on excretion of JBP485 via organic anion transporters in rats. Eur J Pharm Sci 48:351–359CrossRefPubMedGoogle Scholar
  100. Milde P, Hauser U, Simon T, Mall G, Ernst V, Haussler MR, Frosch P, Rauterberg EW (1991) Expression of 1,25-dihydroxyvitamin D3 receptors in normal and psoriatic skin. J Invest Dermatol 97:230–239CrossRefPubMedGoogle Scholar
  101. Miyachi Y, Ohkawara A, Ohkido M, Harada S, Tamaki K, Nakagawa H, Hori Y, Nishiyama S (2002) Long-term safety and efficacy of high-concentration (20 microg/g) tacalcitol ointment in psoriasis vulgaris. Eur J Dermatol 12:463–468PubMedGoogle Scholar
  102. Monier-Faugere MC, Geng Z, Friedler RM, Qi Q, Kubodera N, Slatopolsky E, Malluche HH (1999) 22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure. Kidney Int 55:821–832CrossRefPubMedGoogle Scholar
  103. Morán-Auth Y, Penna-Martinez M, Shoghi F, Ramos-Lopez E, Badenhoop K (2013) Vitamin D status and gene transcription in immune cells. J Steroid Biochem Mol Biol 136:83–85CrossRefPubMedGoogle Scholar
  104. Muto A, Kizaki M, Yamato K, Kawai Y, Kamata-Matsushita M, Ueno H, Ohguchi M, Nishihara T, Koeffler HP, Ikeda Y (1999) 1,25-Dihydroxyvitamin D3 induces differentiation of a retinoic acid-resistant acute promyelocytic leukemia cell line (UF-1) associated with expression of p21(WAF1/CIP1) and p27(KIP1). Blood 93:2225–2233PubMedGoogle Scholar
  105. Nakagawa K, Kawaura A, Kato S, Takeda E, Okano T (2005) 1 α,25-Dihydroxyvitamin D(3) is a preventive factor in the metastasis of lung cancer. Carcinogenesis 26:429–440CrossRefPubMedGoogle Scholar
  106. Narvaez CJ, Matthews D, LaPorta E, Simmons KM, Beaudin S, Welsh J (2014) The impact of vitamin D in breast cancer: genomics, pathways, metabolism. Front Physiol 5:213CrossRefPubMedPubMedCentralGoogle Scholar
  107. Naveh-Many T, Silver J (1993) Effects of calcitriol, 22-oxacalcitriol, and calcipotriol on serum calcium and parathyroid hormone gene expression. Endocrinology 133:2724–2728CrossRefPubMedGoogle Scholar
  108. Naveilhan P, Berger F, Haddad K, Barbot N, Benabid AL, Brachet P, Wion D (1994) Induction of glioma cell death by 1,25(OH)2 vitamin D3: towards an endocrine therapy of brain tumors? J Neurosci Res 37:271–277CrossRefPubMedGoogle Scholar
  109. Nemerovski CW, Dorsch MP, Simpson RU, Bone HG, Aaronson KD, Bleske BE (2009) Vitamin D and cardiovascular disease. Pharmacotherapy 29:691–708CrossRefPubMedGoogle Scholar
  110. Nibbelink KA, Tishkoff DX, Hershey SD, Rahman A, Simpson RU (2007) 1,25(OH)2-vitamin D3 actions on cell proliferation, size, gene expression, and receptor localization, in the HL-1 cardiac myocyte. J Steroid Biochem Mol Biol 103:533–537CrossRefPubMedGoogle Scholar
  111. Nishizawa Y, Morii H, Ogura Y, De Luca HF (1991) Clinical trial of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 in uremic patients on hemodialysis: preliminary report. Contrib Nephrol 90:196–203CrossRefPubMedGoogle Scholar
  112. Okamoto R, Delansorne R, Wakimoto N, Doan NB, Akagi T, Shen M, Ho QH, Said JW, Koeffler HP (2012) Inecalcitol, an analog of 1α,25(OH)(2) D(3), induces growth arrest of androgen-dependent prostate cancer cells. Int J Cancer 130:2464–2473CrossRefPubMedGoogle Scholar
  113. Pálmer HG, Sánchez-Carbayo M, Ordóñez-Morán P, Larriba MJ, Cordón-Cardó C, Muñoz A (2003) Genetic signatures of differentiation induced by 1α,25-dihydroxyvitamin D3 in human colon cancer cells. Cancer Res 63:7799–7806PubMedGoogle Scholar
  114. Papadimitropoulos E, Wells G, Shea B, Gillespie W, Weaver B, Zytaruk N, Cranney A, Adachi J, Tugwell P, Josse R, Greenwood C, Guyatt G, Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women. Endocr Rev 23:560–569CrossRefPubMedPubMedCentralGoogle Scholar
  115. Park MR, Lee JH, Park MS, Hwang JE, Shim HJ, Cho SH, Chung IJ, Bae WK (2012) Suppressive effect of 19-nor-1α-25-dihydroxyvitamin D2 on gastric cancer cells and peritoneal metastasis model. J Korean Med Sci 27:1037–1043CrossRefPubMedPubMedCentralGoogle Scholar
  116. Peleg S, Uskokovic M, Ahene A, Vickery B, Avnur Z (2002) Cellular and molecular events associated with the bone-protecting activity of the noncalcemic vitamin D analog Ro-26-9228 in osteopenic rats. Endocrinology 143:1625–1636CrossRefPubMedGoogle Scholar
  117. Pendás-Franco N, García JM, Peña C, Valle N, Pálmer HG, Heinäniemi M, Carlberg C, Jiménez B, Bonilla F, Muñoz A, González-Sancho JM (2008) DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1α,25-dihydroxyvitamin D3. Oncogene 27:4467–4477CrossRefPubMedGoogle Scholar
  118. Pepper C, Thomas A, Hoy T, Milligan D, Bentley P, Fegan C (2003) The vitamin D3 analog EB1089 induces apoptosis via a p53-independent mechanism involving p38 MAP kinase activation and suppression of ERK activity in B-cell chronic lymphocytic leukemia cells in vitro. Blood 101:2454–2460CrossRefPubMedGoogle Scholar
  119. Pèrez A, Chen TC, Turner A, Raab R, Bhawan J, Poche P, Holick MF (1996) Efficacy and safety of topical calcitriol (1,25-dihydroxyvitamin d3) for the treatment of psoriasis. Br J Dermatol 134:238–246CrossRefPubMedGoogle Scholar
  120. Pierrot-Deseilligny C, Rivaud-Péchoux S, Clerson P, de Paz R, Souberbielle JC (2012) Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation. Ther Adv Neurol Disord 5:187–198CrossRefPubMedPubMedCentralGoogle Scholar
  121. Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, März W (2008a) Low vitamin d levels predict stroke in patients referred to coronary angiography. Stroke 39:2611–2613CrossRefPubMedGoogle Scholar
  122. Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, Boehm BO, Dobnig H (2008b) Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab 93:3927–3935CrossRefPubMedGoogle Scholar
  123. Prietl B, Treiber G, Pieber TR, Amrein K (2013) Vitamin D and Immune Function. Nutrients 5:2502–2521CrossRefPubMedPubMedCentralGoogle Scholar
  124. Quach HP, Noh K, Hoi SY, Bruinsma A, Groothuis GMM, Li AP, Chow ECY, Pang KS (2018) Alterations in gene expression in vitamin D-deficiency: Down-regulation of liver Cyp7a1 and renal Oat3 in mice. Biopharm Drug Dispos 39:99–115CrossRefPubMedGoogle Scholar
  125. Rahman A, Hershey S, Ahmed S, Nibbelink K, Simpson RU (2007) Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. J Steroid Biochem Mol Biol 103:416–419CrossRefPubMedGoogle Scholar
  126. Reichrath J (2007) Vitamin D and the skin: an ancient friend, revisited. Exp Dermatol 16:618–625CrossRefPubMedGoogle Scholar
  127. Richy F, Ethgen O, Bruyere O, Reginster JY (2004) Efficacy of αcalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate. Osteoporos Int 15:301–310CrossRefPubMedGoogle Scholar
  128. Rondini EA, Fang H, Runge-Morris M, Kocarek TA (2014) Regulation of human cytosolic sulfotransferases 1C2 and 1C3 by nuclear signaling pathways in LS180 colorectal adenocarcinoma cells. Drug Metab Dispos 42(3):361–368CrossRefPubMedPubMedCentralGoogle Scholar
  129. Rostand SG, Drüeke TB (1999) Parathyroid hormone, vitamin D, and cardiovascular disease in chronic renal failure. Kidney Int 56:383–392CrossRefPubMedGoogle Scholar
  130. Sakai Y, Demay MB (2000) Evaluation of keratinocyte proliferation and differentiation in vitamin D receptor knockout mice. Endocrinology 141:2043–2049CrossRefPubMedGoogle Scholar
  131. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R (2006) Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 83:754–759CrossRefPubMedGoogle Scholar
  132. Schmiedlin-Ren P, Thummel KE, Fisher JM, Paine MF, Lown KS, Watkins PB (1997) Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1α,25-dihydroxyvitamin D3. Mol Pharmacol 51(5):741–754CrossRefPubMedGoogle Scholar
  133. Schwartz JB (2009) Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther 85(2):198–203CrossRefPubMedGoogle Scholar
  134. Schwartz GG, Wang MH, Zang M, Singh RK, Siegal GP (1997) 1α,25-Dihydroxyvitamin D (calcitriol) inhibits the invasiveness of human prostate cancer cells. Cancer Epidemiol Biomarkers Prev 6:727–732PubMedGoogle Scholar
  135. Schwartz GG, Eads D, Naczki C, Northrup S, Chen T, Koumenis C (2008) 19-nor-1 α,25-dihydroxyvitamin D2 (paricalcitol) inhibits the proliferation of human pancreatic cancer cells in vitro and in vivo. Cancer Biol Ther 7:430–436CrossRefPubMedGoogle Scholar
  136. Seubwai W, Wongkham C, Puapairoj A, Okada S, Wongkham S (2010) 22-oxa-1,25-dihydroxyvitamin D3 efficiently inhibits tumor growth in inoculated mice and primary histoculture of cholangiocarcinoma. Cancer 116:5535–5543CrossRefPubMedGoogle Scholar
  137. Shapira Y, Agmon-Levin N, Shoenfeld Y (2010) Geoepidemiology of autoimmune rheumatic diseases. Nat Rev Rheumatol 6:468–476CrossRefPubMedGoogle Scholar
  138. Shedeed SA (2012) Vitamin D supplementation in infants with chronic congestive heart failure. Pediatr Cardiol 33:713–719CrossRefPubMedGoogle Scholar
  139. Shevde NK, Plum LA, Clagett-Dame M, Yamamoto H, Pike JW, DeLuca HF (2002) A potent analog of 1α,25-dihydroxyvitamin D3 selectively induces bone formation. Proc Natl Acad Sci USA 99:13487–13491CrossRefPubMedGoogle Scholar
  140. Simpson RU, Hershey SH, Nibbelink KA (2007) Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol 103:521–524CrossRefPubMedGoogle Scholar
  141. Slatopolsky E, Finch J, Ritter C, Denda M, Morrissey J, Brown A, DeLuca H (1995) A new analog of calcitriol, 19-nor-1,25-(OH)2 D2, suppresses parathyroid hormone secretion in uremic rats in the absence of hypercalcemia. Am J Kidney Dis 26:852–860CrossRefPubMedGoogle Scholar
  142. Slatopolsky E, Cozzolino M, Lu Y, Finch J, Dusso A, Staniforth M, Wein Y, Webster J (2003) Efficacy of 19-Nor-1,25-(OH)2D2 in the prevention and treatment of hyperparathyroid bone disease in experimental uremia. Kidney Int 63:2020–2027CrossRefPubMedGoogle Scholar
  143. So JY, Lee HJ, Smolarek AK, Paul S, Wang CX, Maehr H, Uskokovic M, Zheng X, Conney AH, Cai L, Liu F, Suh N (2011) A novel Gemini vitamin D analog represses the expression of a stem cell marker CD44 in breast cancer. Mol Pharmacol 79:360–367CrossRefPubMedPubMedCentralGoogle Scholar
  144. Soleymani T, Hung T, Soung J (2015) The role of vitamin D in psoriasis: a review. Int J Dermatol 54:383–392CrossRefPubMedGoogle Scholar
  145. Sung V, Feldman D (2000) 1,25-Dihydroxyvitamin D3 decreases human prostate cancer cell adhesion and migration. Mol Cell Endocrinol 164:133–143CrossRefPubMedGoogle Scholar
  146. Sunyecz JA (2008) The use of calcium and vitamin D in the management of osteoporosis. Ther Clin Risk Manag 4:827–836CrossRefPubMedPubMedCentralGoogle Scholar
  147. Tamura S, Ueki K, Mashimo K, Tsukada Y, Naitoh M, Abe Y, Kawai H, Tsuchida A, Wakamatsu R, Nojima Y (2005) Comparison of the efficacy of an oral calcitriol pulse or intravenous 22-oxacalcitriol therapies in chronic hemodialysis patients. Clin Exp Nephrol 9:238–243CrossRefPubMedGoogle Scholar
  148. Thompson PD, Jurutka PW, Whitfield GK, Myskowski SM, Eichhorst KR, Dominguez CE, Haussler CA, Haussler MR (2002) Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Biochem Biophys Res Commun 299(5):730–738CrossRefPubMedGoogle Scholar
  149. Thummel KE, Brimer C, Yasuda K, Thottassery J, Senn T, Lin Y, Ishizuka H, Kharasch E, Schuetz J, Schuetz E (2001) Transcriptional control of intestinal cytochrome P-4503A by 1α,25-dihydroxy vitamin D3. Mol Pharmacol 60:1399–1406CrossRefPubMedGoogle Scholar
  150. Torres A, García S, Gómez A, González A, Barrios Y, Concepción MT, Hernández D, García JJ, Checa MD, Lorenzo V, Salido E (2004) Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation. Kidney Int 65:705–712CrossRefPubMedGoogle Scholar
  151. Trémezaygues L, Reichrath J (2011) Vitamin D analogs in the treatment of psoriasis: Where are we standing and where will we be going? Dermatoendocrinol 3:180–186CrossRefPubMedPubMedCentralGoogle Scholar
  152. Trump DL, Deeb KK, Johnson CS (2010) Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy. Cancer J 16:1–9CrossRefPubMedPubMedCentralGoogle Scholar
  153. van Etten E, Mathieu C (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101CrossRefPubMedGoogle Scholar
  154. van Ginkel PR, Yang W, Marcet MM, Chow CC, Kulkarni AD, Darjatmoko S, Lindstrom MJ, Lokken J, Bhattacharya S, Albert DM (2007) 1 α-Hydroxyvitamin D2 inhibits growth of human neuroblastoma. J Neurooncol 85:255–262CrossRefPubMedGoogle Scholar
  155. van de Kerkhof PC, van Bokhoven M, Zultak M, Czarnetzki BM (1989) A double-blind study of topical 1 α,25-dihydroxyvitamin D3 in psoriasis. Br J Dermatol 120:661–664CrossRefPubMedGoogle Scholar
  156. van de Kerkhof PC, Berth-Jones J, Griffiths CE, Harrison PV, Hönigsmann H, Marks R, Roelandts R, Schöpf E, Trompke C (2002) Long-term efficacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis. Br J Dermatol 146:414–422CrossRefPubMedGoogle Scholar
  157. Walters MR, Ilenchuk TT, Claycomb WC (1987) 1,25-Dihydroxyvitamin D3 stimulates 45Ca2+ uptake by cultured adult rat ventricular cardiac muscle cells. J Biol Chem 262:2536–2541PubMedGoogle Scholar
  158. Wang QM, Jones JB, Studzinski GP (1996) Cyclin-dependent kinase inhibitor p27 as a mediator of the G1-S phase block induced by 1,25-dihydroxyvitamin D3 in HL60 cells. Cancer Res 56:264–267PubMedGoogle Scholar
  159. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511CrossRefPubMedGoogle Scholar
  160. Wang X, Wang H, Shen B, Overholser BR, Cooper BR, Lu Y, Tang H, Zhou C, Sun X, Zhong L, Favus MJ, Decker BS, Liu W, Peng Z (2016) 1-A, 25-dihydroxyvitamin D3 alters the pharmacokinetics of mycophenolic acid in renal transplant recipients by regulating two extrahepatic UDP-glucuronosyltransferases 1A8 and 1A10. Transl Res 178:54–62CrossRefPubMedGoogle Scholar
  161. Weishaar RE, Simpson RU (1987a) Involvement of vitamin D3 with cardiovascular function. II. Direct and indirect effects. Am J Physiol 253:E675–E683PubMedGoogle Scholar
  162. Weishaar RE, Simpson RU (1987b) Vitamin D3 and cardiovascular function in rats. J Clin Invest 79:1706–1712CrossRefPubMedPubMedCentralGoogle Scholar
  163. Weishaar RE, Kim SN, Saunders DE, Simpson RU (1990) Involvement of vitamin D3 with cardiovascular function. III. Effects on physical and morphological properties. Am J Physiol 258:E134–E142PubMedGoogle Scholar
  164. Welsh J, Wietzke JA, Zinser GM, Byrne B, Smith K, Narvaez CJ (2003) Vitamin D-3 receptor as a target for breast cancer prevention. J Nutr 133:2425S–2433SCrossRefPubMedGoogle Scholar
  165. Wöbke TK, Sorg BL, Steinhilber D (2014) Vitamin D in inflammatory diseases. Front Physiol 5:244PubMedPubMedCentralGoogle Scholar
  166. Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YC (2005) Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 288:E125–E132CrossRefPubMedGoogle Scholar
  167. Xu Y, Iwanaga K, Zhou C, Cheesman MJ, Farin F, Thummel KE (2006) Selective induction of intestinal CYP3A23 by 1α,25-dihydroxyvitamin D3 in rats. Biochem Pharmacol 28:385–392CrossRefGoogle Scholar
  168. Yasuda M, Akiba T, Nihei H (2003) Multicenter clinical trial of 22-oxa-1,25-dihydroxyvitamin D3 for chronic dialysis patients. Am J Kidney Dis 41:S108–S111CrossRefPubMedGoogle Scholar
  169. Yoon IS, Son JH, Kim SB, Choi MK, Maeng HJ (2015) Effects of 1α,25-Dihydroxyvitamin D3 on intestinal absorption and disposition of adefovir dipivoxil and its metabolite, adefovir, in Rats. Biol Pharm Bull 38:1732–1737CrossRefPubMedGoogle Scholar
  170. Yudoh K, Matsuno H, Kimura T (1999) 1α,25-dihydroxyvitamin D3 inhibits in vitro invasiveness through the extracellular matrix and in vivo pulmonary metastasis of B16 mouse melanoma. J Lab Clin Med 133:120–128CrossRefPubMedGoogle Scholar
  171. Zhang Y, Zhang J, Studzinski GP (2006) AKT pathway is activated by 1, 25-dihydroxyvitamin D3 and participates in its anti-apoptotic effect and cell cycle control in differentiating HL60 cells. Cell Cycle 5:447–451CrossRefPubMedGoogle Scholar
  172. Zhang H, Shih DQ, Zhang X (2013) Mechanisms underlying effects of 1,25-Dihydroxyvitamin D3 on the Th17 cells. Eur J Microbiol Immunol (Bp) 3:237–240CrossRefGoogle Scholar
  173. Zhuang SH, Burnstein KL (1998) Antiproliferative effect of 1α,25-dihydroxyvitamin D3 in human prostate cancer cell line LNCaP involves reduction of cyclin-dependent kinase 2 activity and persistent G1 accumulation. Endocrinology 139:1197–1207CrossRefPubMedGoogle Scholar
  174. Zierold C, Mings JA, Deluca HF (2006) 19nor-1,25-dihydroxyvitamin D2 specifically induces CYP3A9 in rat intestine more strongly than 1,25-dihydroxyvitamin D3 in vivo and in vitro. Mol Pharmacol 69:1740–1747CrossRefPubMedGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2019

Authors and Affiliations

  1. 1.Lab of Pharmacology, College of PharmacyDongduk Women’s UniversitySeoulRepublic of Korea
  2. 2.Department of Pharmaceutical EngineeringInje UniversityGimhaeRepublic of Korea
  3. 3.College of PharmacyGachon UniversityIncheonRepublic of Korea

Personalised recommendations