Study: EGCG and Colon Cancer

GIFU, JapanIt's been previously reported that ()-epigallocatechin gallate (EGCG) in green tea alters plasma membrane organization and causes internalization of epidermal growth factor receptor (EGFR), resulting in the suppression of colon cancer cell growth. A recent study found the mechanism underlying EGCG-induced downregulation of EGFR colon cancer cells was due to phosphorylation of EGFR. (Carcinogenesis 2009) (DOI:10.1093/carcin/bgp166). Prolonged exposure to EGCG caused EGFR degradation. However, EGCG required neither an ubiquitin ligase (c-Cbl) binding to EGFR nor phosphorylation of EGFR at tyrosine residues, both of which are reportedly necessary for EGFR degradation induced by EGF. In addition, EGCG induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), a stress-inducible kinase believed to negatively regulate tumorigenesis, and the inhibition of p38 MAPK by SB203580, a specific p38 MAPK inhibitor, or the gene silencing using p38 MAPK-siRNA suppressed the internalization and subsequent degradation of EGFR induced by EGCG. EGFR underwent a gel mobility shift upon treatment with EGCG and this was canceled by SB203580, indicating EGCG causes EGFR phosphorylation via p38 MAPK. EGCG caused phosphorylation of EGFR at Ser1046/1047, a site which is critical for its downregulation and this was also suppressed by SB203580 or siRNA of p38 MAPK.