KMID : 0613820060160060964
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Journal of Life Science 2006 Volume.16 No. 6 p.964 ~ p.971
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Inhibitory Effects of Type ¥³ Collagenase by Disulfiram
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Shin Doo-Il
Park Jae-Bok Park Kwan-Kyu Cho Chang-Ho Oh Hoon-Kyu Choi Chang-Hyuk Cho Hyun-Ji Chang Young-Chae
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Abstract
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The cancer cells, characterized by local invasion and distant metastasis, are very dependant on extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. Among the human MMPs, matirx metalloproteinase-2 (MMP-2) and matrix metalloproteinse-9 (MMP-9) are key enzymes that degrade type IV collagen of the matrix. Here, we studied the effect of disulfiram, an anti-tumor compound, on the suppression of the tumor invasion and the activity of MMP-2, MMP-9 in human osteosarcoma cells (U2OS). Disulfiram had the type IV collagenase inhibitory activity, the effect of inhibition of gene and protein expression, and these inhibitions were responsible for blocking invasion through cell mediated and non-cell mediated pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9, and regulated the invasion of U2OS, Caki-1 and Caski. These observations raise the possibility of clinical therapeutic applications for disulfiram used as a potential inhibitor of cancer invasion.
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KEYWORD
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Disulfiram, PMA, MMP-9, MMP-2, anti-Cancer
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