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

Hideya Mizuno, Yong Yeon Cho, Feng Zhu, Wei Ya Ma, Ann M. Bode, Chung S. Yang, Chi Tang Ho, Zigang Dong

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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-Za), 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 CI41 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.

Original languageEnglish (US)
Pages (from-to)204-212
Number of pages9
JournalMolecular Carcinogenesis
Volume45
Issue number3
DOIs
StatePublished - Mar 2006

Keywords

  • A431 human epidermoid carcinoma
  • Anchorage-independent cell transformation
  • JB6 CI41 mouse epidermal cells
  • Theaflavins

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