Glycitein inhibits glioma cell invasion through down-regulation of MMP-3 and MMP-9 gene expression

Eun Jung Lee, So Young Kim, Jin Won Hyun, Sung Won Min, Dong Hyun Kim, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that play a pivotal role in invasion and angiogenesis of malignant glioma cells. Therefore, the inhibition of MMPs has been suggested to be a promising therapeutic strategy for brain tumors. In the present study, we found that glycitein, a bacterial metabolite of the isoflavone glycitin, inhibits the expression of MMP-3 and MMP-9 at promoter, mRNA, and protein levels in PMA-stimulated U87MG human astroglioma cells. In addition, gelatin zymography showed that glycitein inhibited the PMA-induced MMP-9 secretion in U87MG cells. A subsequent Matrigel invasion assay revealed that glycitein suppresses the in vitro invasiveness of glioma cells, which may be at least partly due to the glycitein-mediated inhibition of MMP-3 and MMP-9. In support of this, treatment of MMP-3- or MMP-9-specific inhibitor significantly suppressed PMA-induced invasion of glioma cells. Further mechanistic studies revealed that glycitein inhibits the DNA binding and transcriptional activities of NF-κB and AP-1, which are important transcription factors for MMP-3 or MMP-9 gene expression. Furthermore, glycitein suppresses PMA-induced phosphorylation of three types of MAP kinases, which are upstream signaling molecules in MMP gene expressions and NF-κB and AP-1 activities in glioma cells. Therefore, the inhibition of MMP-3 and MMP-9 expression by glycitein may have therapeutic potential for controlling invasiveness of malignant gliomas.

Original languageEnglish
Pages (from-to)18-24
Number of pages7
JournalChemico-Biological Interactions
Volume185
Issue number1
DOIs
StatePublished - Apr 2010

Keywords

  • Gene regulation
  • Glioma
  • Glycitein
  • Invasion
  • MMP-3
  • MMP-9

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