Abstract
Matrix metalloproteinase-9 (MMP-9) plays an important role in mediating the invasion and angiogenic process of malignant gliomas. This study was undertaken to determine if an isoflavone metabolite, irisolidone, inhibits MMP-9 expression in human astroglioma cells. Irisolidone was found to inhibit the secretion and protein expression of MMP-9 induced by PMA in U87 MG glioma cells, accompanied by the inhibition of MMP-9 mRNA expression and promoter activity. Further mechanistic studies revealed that irisolidone inhibits the binding of NF-κB and AP-1 to the MMP-9 promoter and suppresses the PMA-induced phosphorylation of ERK and JNK, which are upstream signaling molecules in MMP-9 expression. The Matrigel-invasion assay showed that irisolidone suppresses the in vitro invasiveness of glioma cells. Therefore, the strong inhibition of MMP-9 expression by irisolidone might be a potential therapeutic modality for controlling the growth and invasiveness of gliomas.
Original language | English |
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Pages (from-to) | 493-499 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 366 |
Issue number | 2 |
DOIs | |
State | Published - 8 Feb 2008 |
Bibliographical note
Funding Information:This work was supported by the Korea Research Foundation Grant funded by the Korean Government (2006-KFR-531-E00060), and in part by Neurobiology Research Program (M10412000042-04N1200 -04210) of the Ministry of Science and Technology, Republic of Korea.
Keywords
- AP-1
- Glioma
- Invasion
- Irisolidone
- MMP-9
- NF-κB
- Signaling pathways