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

✍ Scribed by Hideya Mizuno; Yong-Yeon Cho; Feng Zhu; Wei-Ya Ma; Ann M. Bode; Chung S. Yang; Chi-Tang Ho; Zigang Dong

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 342 KB
• Volume: 45
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20174

✦ Synopsis

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. © 2005 Wiley‐Liss, Inc.