Suppression of extracellular signals and cell proliferation through EGF receptor binding by (-)-epigallocatechin gallate in human A431 epidermoid carcinoma cells

Yu Chih Liang, Shoei Yn Lin-shiau, Chieh Fu Chen, Jen Kun Lin

Research output: Contribution to journalArticle

275 Citations (Scopus)

Abstract

Tea polyphenols are known to inhibit a wide variety of enzymatic activities associated with cell proliferation and tumor progression. The molecular mechanisms of antiproliferation are remained to be elucidated. In this study, we investigated the effects of the major tea polyphenol (-)- epigallocatechin gallate (EGCG) on the proliferation of human epidermoid carcinoma cell line, A431. Using a [3H]thymidine incorporation assay, EGCG could significantly inhibit the DNA synthesis of A431 cells. In vitro assay, EGCG strongly inhibited the protein tyrosine kinase (PTK) activities of EGF- R, PDGF-R, and FGF-R, and exhibited an IC50 value of 0.5-1 μg/ml. But EGCG scarcely inhibited the protein kinase activities of pp60(v-src), PKC, and PKA (IC50 > 10 μg/ml). In an in vivo assay, EGCG could reduce the autophosphorylation level of EGF-R by EGR. Phosphoamino acid analysis of the EGF-R revealed that EGCG inhibited the EGF-stimulated increase in phosphotyrosine level in A431 cells. In addition, we showed that EGCG blocked EGF binding to its receptor. The results of further studies suggested that the inhibition of proliferation and suppression of the EGF signaling by EGCG might mainly mediate dose-dependent blocking of ligand binding to its receptor, and subsequently through inhibition of EGF-R kinase activity.

Original languageEnglish
Pages (from-to)55-65
Number of pages11
JournalJournal of Cellular Biochemistry
Volume67
Issue number1
DOIs
Publication statusPublished - Oct 1 1997
Externally publishedYes

Keywords

  • (-)-Epigallocatechin gallate
  • Epidermal growth factor receptor
  • Fibroblast growth factor
  • Platelet- derived growth factor
  • Protein kinase A
  • Protein kinase C
  • Protein tyrosine kinases
  • Receptor tyrosine kinases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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