Preferences help
enabled [disable] Abstract
Number of results
2009 | 56 | 2 | 235-242
Article title

Influence of vitamin D3 analogues in combination with budesonid R on proliferation of nasal polyp fibroblasts

Title variants
Languages of publication
Vitamin D (VD) and its different analogues, besides their classic role as regulators of calcium and phosphor homeostasis, have emerged as a large family of antiproliferative agents. Such properties suggested VD potential as a therapy for chronic inflammatory diseases, including nasal polyposis (NP). NP growth involves both an inflammatory process and the proliferation of fibroblast as an important factor inducing aberrations in the phenotype of the epithelium. The aim of this study was to investigate the possible influence of 1α,25-dihydroxyvitamin D3 (calcitriol) and 1α,24(R)-dihydroxyvitamin D3 (tacalcitol) in monotherapy and in combination with budesonid R (BR) on NP fibroblast proliferation. Material and methods: The study involved 26 samples of NP. NP cells were cultured on 96-well plates beginning with a concentration of 5 × 103 cells per well with RPMI 1640 medium supplemented with antibiotics and 10% foetal bovine serum. After the fourth to sixth passage the medium was replaced with a nutrient medium with calcitriol or tacalcitol in a defined concentration (from 10-9 M to 10-3 M) alone or in combination with BR in 1:1, 1:3 or 3:1 ratios, each at concentrations from 10-5 M to 10-3 M. Results: Growth inhibition of nasal fibroblasts exposed to calcitriol or tacalcitol was noted. Significant antiproliferating activity was observed at calcitriol concentrations of 10-4 M and 10-3 M after 48 h, and at a concentration of 10-3 M after 72 h with the percentage of proliferating cells reduced to 30% compared to the control samples (P < 0.05). In cells treated with tacalcitol the maximal effect was seen at 10-4 M after 48 h and at 10-3M after 72 h with a 60% inhibition with respect to the control (P < 0.05). The inhibition of fibroblast proliferation reached the maximal level when they were exposed to calcitriol: BR (1 : 1) or tacalcitol: BR (1 : 1), each at a concentration of 10-4 M, after 72 h (82% and 69%, respectively). Conclusions: The antiproliferative activity of calcitriol and tacalcitol in NP cultures was confirmed. Because of its lower toxicity and higher activity tacalcitol seems to be the more promising agent in NP therapy, both as a single medication and in treatment protocols with BR.
Physical description
  • Department of Otolaryngology Head & Neck Surgery, Wroclaw Medical University, Wrocław, Poland
  • Department of Otolaryngology Head & Neck Surgery, Wroclaw Medical University, Wrocław, Poland
  • Department of Otolaryngology Head & Neck Surgery, Wroclaw Medical University, Wrocław, Poland
  • Department of Molecular Biology and Medical Genetics, Medical University of Silesia, Katowice, Poland
  • Audo I, Darjatmoko SR, Schlamp CL, Lokken JM, Lindstrom MJ, Albert DM (2003) Vitamin D analogues increase p53, p21, and apoptosis in a xenograft model of human retinoblastoma. Invest Ophthalmol Vis Sci 44: 4192-4199.
  • Bernardi RJ, Trump DL, Yu WD, McGuire TF, Hershberger PA, Johnson CS (2001) Combination of 1α,25-dihydroxyvitamin D3 with dexamethasone enhances cell cycle arrest and apoptosis: role of nuclear receptor cross-talk and Erk/Akt signaling. Clin Cancer Res 7: 4164-4173.
  • Evans RM (1998) The steroid and thyroid hormone receptor superfamily. Science 240: 889-895.
  • Fukuoka M, Ogino Y, Sato H, Ohta T, Komoriya K (1998) Regulation of RANTES and IL-8 production in normal human dermal fibroblasts by active vitamin D3 (tacalcitol). Br J Pharmacol 124: 1433-1438.
  • Gniadecki R (1996) Stimulation versus inhibition of keratinocytes growth by 1,25-dihydroxyvitamin D3: dependence on cell culture condition. J Invest Dermatol 106: 510-516.
  • Gruber BM, Anuszewska EL (2002) Influence of vitamin D3 metabolites on cell proliferation and cytotoxicity of adriamycin in human normal and neoplastic cells. Toxicol In Vitro 16: 663-667.
  • Hansen CM, Mäenpää PH (1997) EB 1089, a novel vitamin D analog with strong antiproliferative and differentiation-inducing effects on target cells. Biochem Pharmacol 54: 1173-1179.
  • Hershberger PA, Modzelewski RA, Shurin ZR, Rueger RM, Trump DL, Johnson CS (1999) 1,25-Dihydroxycholecalciferol (1,25-D3) inhibits the growth of squamous cell carcinoma and down-modulates p21(Waf1/Cip1) in vitro and in vivo. Cancer Res 59: 2644-2649.
  • Holick MF (1984) The photobiology of vitamin D3 in man In Vitamin D: Basic and Clinical Aspects. Kuman R, ed, pp 197-216. Martinus Nijhoff Boston.
  • James SY, Mackay AG, Colston KW (1996) Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol 58: 395-401.
  • Johnson CS, Hershberger PA, Trump DL (2002) Vitamin D-related therapies in prostate cancer. Cancer Metastasis Rev 21: 147-158.
  • Koli K, Keski-Oja J (1995) 1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells. Cancer Res 55: 1540-1546.
  • Lebwohl M, Menter A, Weiss J, Clark SD, Flores J, Powers J, Balin AK, Kempers S, Glinert RJ, Fleming T, Liu Y, Graeber M, Pariser DM (2007) Calcitriol 3 microg/g ointment in the management of mild to moderate plaque type psoriasis: results from 2 placebo-controlled, multicenter, randomized double-blind, clinical studies. J Drugs Dermatol 6: 428-435.
  • Leone G, Pacifico A (2005) Profile of clinical efficacy and safety of topical tacalcitol. Acta Biomed 76: 13-19.
  • MacDonald PN, Baudino TA, Tokumaru H, Dowd DR, Zhang C (2001) Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription. Steroids 66: 171-176.
  • McGuire TF, Trump DL, Johnson CS (2001) Vitamin D3-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: 26365-26373.
  • 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: 533-537.
  • Norlander T, Brönnegård M, Stierna P (1999) The relationship of nasal polyps, infection, and inflammation. Am J Rhinol 13: 349-355.
  • Pawankar R (2003) Nasal polyposis: an update: editorial review. Curr Opin Allergy Clin Immunol 3: 1-6.
  • Pourgholami MH, Akhter J, Lu Y, Morris DL (2000) In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Lett 151: 97-102.
  • Rinia AB, Kostamo K, Ebbens FA, van Drunen CM, Fokkens WJ (2007) Nasal polyposis: a cellular-based approach to answering questions. Allergy 62: 348-358.
  • Rocker D, Ravid A, Liberman UA, Garach-Jehoshua O, Koren R (1994) 1,25-Dihydroxyvitamin D3 potentiates the cytotoxic effect of TNF on human breast cancer cells. Mol Cell Endocrinol 106: 157-162.
  • Rostkowska-Nadolska B, Szymaniec S, Fortuna W, Szelejewski W, Uszycka-Horawa T, Zakrzewska-Karniewicz H (2002) Patent Number P-358032 (Zastosowanie 22R-16α,17α-butylidenodioksy-11-β,21-dihydroksy-1,4-pregnadien-3,20-dionu jako środka antyproliferacyjnego w terapii polipów nosowych. Zgłoszenie patentowe numer P-358032; in Polish).
  • Rostkowska-Nadolska B, Preś K, Orendorz-Frączkowska K (2005) 22R-16α, 17α-butylidenodioxy-11β,21-dihydroxy-1,4-pregnadien-3,20-dione - nasal water spray in prevention and treatment nasal polyposis. Adv Clin Exp Med 14: 497-503.
  • Ruzicka T, Trompke C (2004) Treatment of scalp psoriasis. An effective and safe tacalcitol emulsion. Hautarzt 55: 165-170.
  • Saunders DE, Christensen C, Wappler NL, Schultz JF, Lawrence WD, Malviya VK (1993) Inhibition of c-myc in breast and ovarian carcinoma cells by 1,25-dihydroxyvitamin D3, retinoic acid and dexamethasone. Anticancer Drugs 4: 201-208.
  • Sprenger CC, Peterson A, Lance R, Ware JL, Drivdahl RH, Plymate SR (2001) Regulation of proliferation of prostate epithelial cells by 1,25-dihydroxyvitamin D3 is accompanied by an increase in insulin-like growth factor binding protein-3. J Endocrinol 170: 609-618.
  • Takahashi H, Ibe M, Kinouchi M, Ishida-Yamamoto A, Hashimoto Y, Iizuka H (2003) Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation. J Dermatol Sci 31: 21-28.
  • Wu G, Fan RS, Li W, Ko TC, Brattain MG (1997) Modulation of cell cycle control by vitamin D3 and its analogue, EB 1089, in human breast cancer cells. Oncogene 15: 1555-1563.
  • Yu WD, McElwain MC, Modzelewski RA (1998) Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone. J Natl Cancer Inst 90: 134-141.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.