title: Suppressive effect of calcipotriol on the induction of matrix metalloproteinase (MMP)-9 and MMP-13 in a human squamous cell carcinoma cell line.
abstract: BACKGROUND
  Vitamin D3 is a potent regulator of cell growth, differentiation and death, tumour invasion, and angiogenesis. Production of matrix metalloproteinase (MMP)-9 and MMP-13 by tumour cells may promote tumour growth, invasion and metastasis.
  
  
  OBJECTIVE
  To investigate whether calcipotriol could suppress the expression of MMP-9 and MMP-13 in a human squamous cell carcinoma (SCC) cell line (DJM cells), and to examine the mechanism of modulation of MMP-9 and MMP-13 by calcipotriol in DJM cells treated with tumour necrosis factor (TNF)-α.
  
  
  METHODS
  Protein and mRNA levels of MMP-9 and MMP-13 were examined by ELISA and real-time PCR, respectively. Activation of signalling cascades was assessed using several inhibitors of signalling molecules and western blot analysis.
  
  
  RESULTS
  Production of MMP-9 and MMP-13 markedly increased when the cells were treated with TNF-α. Calcipotriol suppressed the production of MMP-9 and MMP-13 mRNA and proteins significantly, in a dose-dependent manner. Induction of MMP-9 by TNF-α was suppressed by an extracellular signal-regulated kinase (ERK) inhibitor but not by a p38 inhibitor, whereas induction of MMP-13 was inhibited by a p38 inhibitor but not by an ERK inhibitor. Calcipotriol inhibited the phosphorylation of both ERK and p38, as shown by western blotting.
  
  
  CONCLUSIONS
  Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively.
authors.affiliation: Department of Dermatology, Jichi Medical University, Tochigi, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Meephansan
authors.forename: M
authors.initials: M
authors.lastname: Komine
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: M
authors.initials: M
authors.lastname: Ohtsuki
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C055085:calcipotriene; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9; D002117:Calcitriol