title: Inhibition of gap junctional intercellular communication by the green tea polyphenol (-)-epigallocatechin gallate in normal rat liver epithelial cells.
abstract: (-)-Epigallocatechin gallate (EGCG), a polyphenolic compound found in green tea, is a promising chemopreventive agent against cancer due to its strong antiproliferative effects on cancer cells; however, its possible toxicity and carcinogenicity must be investigated before EGCG can be used as a dietary supplement for chemoprevention. The inhibition of gap junctional intercellular communication (GJIC) is strongly associated with carcinogenesis, particularly the tumor promotion process; thus, we investigated the effects of EGCG on GJIC in WB-F344 normal rat liver epithelial (RLE) cells. EGCG, but not (-)-epicatechin (EC), another polyphenol found in green tea, inhibited GJIC in a dose-dependent and reversible manner in RLE cells. EGCG also induced the phosphorylation of connexin 43 (Cx43), a major regulator of GJIC. The phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) was also observed in EGCG-treated RLE cells. The inhibition of GJIC and phosphorylation of Cx43 and ERK1/2 by EGCG were completely blocked by U0126, a pharmacological inhibitor of mitogen-activated protein kinase/ERK kinase. EGCG generated a larger amount of hydrogen peroxide than EC in a dose-dependent manner. Furthermore, catalase partially inhibited the EGCG-induced inhibition of GJIC and the phosphorylation of Cx43 and ERK1/2. These results indicated that EGCG inhibited GJIC mainly due to its prooxidant activity.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Nam Joo
authors.initials: NJ
authors.lastname: Kang
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Jong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Bo Kyung
authors.initials: BK
authors.lastname: Lee
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kwon
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D059808:Polyphenols; D051381:Rats; D013662:Tea / Q000737:chemistry*
chemical_list: D018031:Connexin 43; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D048052:Mitogen-Activated Protein Kinase 3