Tumor gelatinases and invasion inhibited by the green tea flavanol epigallocatechin-3-gallate

Spiridione Garbisa, Luigi Sartor, Susan Biggin, Benedetto Salvato, Roberto Benelli, Adriana Albini

Research output: Contribution to journalArticlepeer-review


BACKGROUND. Given the association of consumption of green tea with prevention of cancer development, metastasis, and angiogenesis, the effect of the main flavanol present, epigallocatechin-3-gallate (EGCG), on two gelatinases most frequently overexpressed in cancer and angiogenesis (MMP-2 and MMP-9) and on tumor cell invasion and chemotaxis were examined. METHODS. Zymography, Western blotting, and enzyme linked immuoadsorbent assay were used to analyze the effect of EGCG on MMP-2 and MMP-9 activity, whereas its effect on tumor cell invasion and chemotaxis was examined using modified Boyden chamber assays. RESULTS. A Zn2+ chelation-independent, dose-dependent, noncompetitive inhibition by EGCG of both gelatinases was found at concentrations 500 times lower than that reported to inhibit urokinase. Tumor cell invasion of a reconstituted basement membrane matrix, but not chemotaxis, was reduced by 50% with EGCG concentrations equivalent to that in the plasma of moderate green tea drinkers, and 2 orders of magnitude below those of tissue inhibitors of MMPs. Although higher concentrations of EGCG were associated with increased levels of both cell-associated gelatinases and their activator MT1-MMP, no increased gelatinase activation was found, and TIMP-1 and TIMP-2 inhibitors were up-regulated. Finally, concentrations of EGCG active in restraining proliferation and inducing apoptosis of transformed cells were more than 100 times lower than those reported for normal cells. CONCLUSI0NS. Epigallocatechin-3-gallate is a potent inhibitor of gelatinases and an orally available pharmacologic agent that may confer the antiangiogenic and antimetastatic activity associated with green tea.

Original languageEnglish
Pages (from-to)822-832
Number of pages11
Issue number4
Publication statusPublished - Feb 15 2001


  • Epigallocatechin-3-gallate (EGCG)
  • Green tea
  • MMP-2
  • MMP-9
  • Tumor invasion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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