J Meephansan1, M Komine, H Tsuda, M Ohtsuki.
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. AIM: 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.
CONCLUSION: Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively. © The Author(s). CED
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. AIM: 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.
CONCLUSION: Calcipotriol reduces MMP-9 and MMP-13 production through inhibiting the phosphorylation of ERK and p38, respectively. © The Author(s). CED
© 2012 British Association of Dermatologists.
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Year: 2012
PMID： 22924547 DOI： 10.1111/j.1365-2230.2012.04381.x
Source DB: PubMed Journal: Clin Exp Dermatol ISSN： 0307-6938 Impact factor: 3.470