Theaflavin-3, 3'-digallate induces epidermal growth factor receptor downregulation

Mol Carcinog. 2006 Mar;45(3):204-12. doi: 10.1002/mc.20174.


Black tea is one of the most popular beverages worldwide and especially in Western nations. Theaflavins, a mixture of theaflavin (TF-1), theaflavin-3-gallate (TF-2a), theaflavin-3'-gallate (TF-2b), and theaflavin-3,3'-digallate (TF-3) are the major components of black tea. Among these black tea components, theaflavin is generally considered to be the more effective component for the inhibition of carcinogenesis. Recently, TF-3 has been shown to have an antiproliferative effect on tumor cells, but the mechanism is not clear. In this study, we showed that TF-3-induced internalization and downregulation of the epidermal growth factor receptor (EGFR). These results suggested that TF-3 induces EGFR endocytosis and degradation. We further showed that TF-3 stimulated EGFR ubiquitination and tyrosine kinase activation. Interestingly, TF-3-induced EGFR downregulation is inhibited by the proteasome inhibitor, MG132, but not by the EGFR-specific receptor tyrosine kinase inhibitor, AG1478. Furthermore, pretreatment with TF-3 inhibited EGF-induced EGFR autophosphorylation, ERKs phosphorylation and AP-1 activation in JB6 Cl41 cells. In addition, TF-3 inhibited EGF-induced anchorage-independent cell transformation. Overall, our results indicate that TF-3 might exert chemopreventive effects through the downregulation of the EGFR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biflavonoids / pharmacology*
  • Carcinoma, Squamous Cell
  • Catechin / pharmacology*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • ErbB Receptors / drug effects
  • ErbB Receptors / genetics*
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology
  • Gene Expression Regulation / drug effects
  • Genes, Reporter
  • Humans
  • Plasmids
  • Tea*
  • Transfection


  • Biflavonoids
  • Tea
  • theaflavin digallate
  • Gallic Acid
  • Catechin
  • ErbB Receptors