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A small compound that inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 upregulation

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Author(s)
권택규
Alternative Author(s)
Kwon, Taeg Kyu
Publication Year
2005
Abstract
Matrix metalloproteinase-9 (MMP-9) is critically involved in the tumor invasion and metastasis processes. Since TNF-α plays a crucial role in the regulation of MMP-9 expression, the development of molecules capable of modulating TNF-α-induced signaling is an issue of concern. We identified a novel synthetic compound that inhibits TNF-α-induced MMP-9 upregulation in the HT1080 human fibrosarcoma cell line. The active compound SM-7368 inhibited TNF-α-induced MMP-9 upregulation in a concentration-dependent manner and showed maximal activity at 10 μM. SM-7368 inhibited TNF-α-induced MMP-9 mRNA transcript accumulation and protein expression. We also found that SM-7368 strongly inhibits TNF-α-induced NF-κB activity but not AP-1 activity. Moreover, we found that SM-7368 strongly inhibits the TNF-α-induced invasion of HT1080 human fibrosarcoma cell line. Taken together, our results demonstrate that SM-7368 is a synthetic compound that inhibits TNF-α-induced MMP-9 expression, and thus SM-7368 should be useful for the development of chemotherapies targeting TNF-α-mediated tumor invasion and metastasis.

Keywords
Matrix metalloproteinase-9;
TNF-α;
Small compound;
NF-κB;
Invasion
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.336(2) : 716-722, 2005
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2005.08.154
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35176
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