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Theaflavin-3, 3'-digallate Induces Epidermal Growth Factor Receptor Downregulation

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

Mol Carcinog. 2006 Mar;45(3):204-12.

PMID: 16353237

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-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP30462352	Theaflavin 3,3′-digallate		30462-35-2	Price

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