Inhibition of matrix metalloproteinase-9 gene expression by an isoflavone metabolite, irisolidone in U87MG human astroglioma cells.

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-kappaB 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.

• Authors: So-Young Kim, Eun-Jung Lee, Moon-Sook Woo, Ji-Sun Jung, Jin-Won Hyun, Sung-Won Min, Dong-Hyun Kim, Hee-Sun Kim
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 366 Issue 2 Pg. 493-9 (Feb 08 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18070596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Flavonoids
• Isoflavones
• NF-kappa B
• Transcription Factor AP-1
• irisolidone
• isoflavanone
• Matrix Metalloproteinase 9

Topics

• Astrocytoma (metabolism)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Flavonoids (administration & dosage)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Isoflavones (administration & dosage, metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• NF-kappa B (metabolism)
• Transcription Factor AP-1 (metabolism)