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Suppressive effect of calcipotriol on the induction of matrix metalloproteinase (MMP)‐9 and MMP‐13 in a human squamous cell carcinoma cell line
Author(s) -
Meephansan J.,
Komine M.,
Tsuda H.,
Ohtsuki M.
Publication year - 2012
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2012.04381.x
Subject(s) - matrix metalloproteinase , calcipotriol , mapk/erk pathway , cell culture , cancer research , angiogenesis , p38 mitogen activated protein kinases , kinase , medicine , microbiology and biotechnology , biology , immunology , genetics , psoriasis
Summary 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.