title: Green tea (-)-epigallocatechin-3-gallate inhibits HGF-induced progression in oral cavity cancer through suppression of HGF/c-Met.
abstract: Hepatocyte growth factor (HGF) and c-Met have recently attracted a great deal of attention as prognostic indicators of patient outcome, and they are important in the control of tumor growth and invasion. Epigallocatechin-3-gallate (EGCG) has been shown to modulate multiple signal pathways in a manner that controls the unwanted proliferation and invasion of cells, thereby imparting cancer chemopreventive and therapeutic effects. In this study, we investigated the effects of EGCG in inhibiting HGF-induced tumor growth and invasion of oral cancer in vitro and in vivo. We examined the effects of EGCG on HGF-induced cell proliferation, migration, invasion, induction of apoptosis and modulation of HGF/c-Met signaling pathway in the KB oral cancer cell line. We investigated the antitumor effect and inhibition of c-Met expression by EGCG in a syngeneic mouse model (C3H/HeJ mice, SCC VII/SF cell line). HGF promoted cell proliferation, migration, invasion and induction of MMP (matrix metalloproteinase)-2 and MMP-9 in KB cells. EGCG significantly inhibited HGF-induced phosphorylation of Met and cell growth, invasion and expression of MMP-2 and MMP-9. EGCG blocked HGF-induced phosphorylation of c-Met and that of the downstream kinases AKT and ERK, and inhibition of p-AKT and p-ERK by EGCG was associated with marked increases in the phosphorylation of p38, JNK, cleaved caspase-3 and poly-ADP-ribose polymerase. In C3H/HeJ syngeneic mice, as an in vivo model, tumor growth was suppressed and apoptosis was increased by EGCG. Our results suggest that EGCG may be a potential therapeutic agent to inhibit HGF-induced tumor growth and invasion in oral cancer.
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon Woo
authors.initials: YW
authors.lastname: Koh
authors.forename: Eun Chang
authors.initials: EC
authors.lastname: Choi
authors.forename: Sung Un
authors.initials: SU
authors.lastname: Kang
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Hwang
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Lee
authors.forename: JungHee
authors.initials: J
authors.lastname: Pyun
authors.forename: RaeHee
authors.initials: R
authors.lastname: Park
authors.forename: YoungDon
authors.initials: Y
authors.lastname: Lee
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018890:Chemoprevention; D018450:Disease Progression; D005260:Female; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D007624:KB Cells; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D009062:Mouth Neoplasms / Q000473:pathology; D009361:Neoplasm Invasiveness; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea
chemical_list: D013662:Tea; D017228:Hepatocyte Growth Factor; D002392:Catechin; C045651:epigallocatechin gallate; D019859:Proto-Oncogene Proteins c-met; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9