A small compound that inhibits tumor necrosis factor-α-induced
matrix metalloproteinase-9 upregulation
- Author(s)
- Ha Young Lee; Kyoung Sun Park; Mi-Kyoung Kim; Taehoon Lee; Sung Ho Ryu; Kyung Jin Woo; Taeg Kyu Kwon; Yoe-Sik Bae
- Keimyung Author(s)
- Kwon, Taeg Kyu
- Department
- Dept. of Immunology (면역학)
- Journal Title
- Biochemical and Biophysical Research Communications
- Issued Date
- 2005
- Volume
- 336
- Issue
- 2
- 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
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