Prostate carcinoma and green tea: (-)Epigallocatechin-3-gallate inhibits inflammation-triggered MMP-2 activation and invasion in murine tramp model

Luigi Sartor, Elga Pezzato, Massimo Donà, Isabella Dell'Aica, Fiorella Calabrese, Monica Morini, Adriana Albini, Spiridione Garbisa

Research output: Contribution to journalArticlepeer-review

Abstract

Green tea infusion has been shown to inhibit metastatic spreading of the transgenic adenocarcinoma of mouse prostate (TRAMP). Investigation on the molecular mechanisms triggered by the main green tea flavonoid, (-)epigallocatechin-3-gallate (EGCG), shows that EGCG restrains TRAMP-CI cell proliferation in a dose-dependent manner, at concentrations (IC50 <0.2 μM) equivalent to those measured in the plasma of moderate green-tea drinkers. Up to 10 μM, EGCG does not modify the cell-surface immuno-localization of MMP-2, one of the invasion-instrumental proteinases; but while in default culture conditions these cells secrete mainly pro-MMP-2, in the presence of reconstituted basement membrane (Matrigel) they release almost exclusively pro-MMP-9. In contrast, when stimulated to traverse Matrigel toward a chemo-attractant, in addition to proMMP-9, they secrete pro-MMP-2. In the presence of 0.2 μM EGCG, only the level of the latter is markedly lowered in the conditioned medium, in parallel with the invasive behavior (>50%). In vivo, s.c. injection of TRAMP-CI cells dispersed in Matrigel gives origin to a tumor mass, whose growth is not inhibited by green-tea regimen. This growth is contained greater than two-thirds by LPS-triggered polymorpho-nuclear phagocyte (PMN) recruitment but this effect is abolished by green tea. Nevertheless, while tumor-released proMMP-2 is activated by co-incubation of TRAMP-CI cells with PMNs, in the presence of 10 μM EGCG the activation is almost abolished. These results suggest that inflammatory involvement of prostate carcinoma could be efficaciously prevented by green tea with a concomitant lowering of the invasive potential.

Original languageEnglish
Pages (from-to)823-829
Number of pages7
JournalInternational Journal of Cancer
Volume112
Issue number5
DOIs
Publication statusPublished - Dec 10 2004

Keywords

  • EGCG
  • Invasion
  • MMP-2 activation
  • Neutrophils
  • Proliferation
  • Prostate carcinoma
  • TRAMP

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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