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Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP

Naoto Oku1, Motomi Matsukawa, Satoru Yamakawa

  • 1Department of Medical Biochemistry and COE Program in the 21st Century, University of Shizuoka, School of Pharmaceutical Sciences.

Biological & Pharmaceutical Bulletin
|September 3, 2003
PubMed

Insights

(-)-Epigallocatechin 3-O-gallate (EGCG), a tea polyphenol, potently inhibits membrane-type 1 matrix metalloproteinase (MT1-MMP). This inhibition suppresses the activation of MMP-2, potentially hindering tumor growth and angiogenesis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Matrix metalloproteinases (MMPs), particularly MT1-MMP, play crucial roles in angiogenesis, tumor cell migration, and metastasis.
  • MT1-MMP is responsible for activating MMP-2, a key enzyme in extracellular matrix remodeling.

Purpose of the Study:

  • To identify specific inhibitors of MT1-MMP from natural and synthetic compounds.
  • To investigate the anti-angiogenic and anti-metastatic potential of identified inhibitors.

Main Methods:

  • Screening of natural and synthetic compounds using recombinant human MMP-2, MMP-7, and soluble MT1-MMP in a fluorogenic peptide cleavage assay.
  • Assessing the inhibitory activity of compounds against MT1-MMP.
  • Evaluating the effect of EGCG on MMP-2 activation in human umbilical vein endothelial cells using gelatin zymography.

Main Results:

  • (-)-Epigallocatechin 3-O-gallate (EGCG) demonstrated potent and specific inhibitory activity against MT1-MMP.
  • EGCG also inhibited the activation of MMP-2 in human umbilical vein endothelial cells.
  • Other related tea polyphenols, such as (-)-epigallocatechin 3,5-di-O-gallate and epitheaflagallin 3-O-gallate, showed inhibitory effects.

Conclusions:

  • EGCG is a potent inhibitor of MT1-MMP and suppresses MMP-2 activation.
  • Tea polyphenols, like EGCG, may suppress tumor growth by inhibiting angiogenesis.
  • These findings highlight the potential of EGCG as a therapeutic agent targeting MT1-MMP in cancer treatment.

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