title: Green tea (-)-epigallocatechin gallate inhibits the growth of human villous trophoblasts via the ERK, p38, AMP-activated protein kinase, and protein kinase B pathways.
abstract: Green tea catechins, especially (-)-epigallocatechin gallate (EGCG), have been reported to circulate in the placenta of animals and blood of humans after consumption. Whether EGCG regulates activity of human villous trophoblasts (HVT) is unknown. This study investigated the pathways involved in EGCG modulation of trophoblast mitogenesis. EGCG inhibited trophoblast proliferation in a dose-dependent and time-dependent manner, as indicated by the number of cells and incorporation of bromodeoxyuridine (BrdU). EGCG was more effective than other green tea catechins in inhibiting cell growth. EGCG also increased the phosphorylation of the MAPK pathway proteins, ERK1/2, and p38, but not JNK. Furthermore, EGCG had no effects on the total amounts of ERK1/2, p38 MAPK, and JNK proteins. This suggests that EGCG selectively affects particular MAPK subfamilies. Pretreatment with specific inhibitors of ERK1/2, p38 MAPK, and AMP-activated protein kinase (AMPK) antagonized EGCG-induced decreases in both cell number and BrdU incorporation. These inhibitors also blocked EGCG-induced increases in the levels of phospho-ERK1/2, phospho-p38, and phospho-AMPK proteins, respectively. Moreover, EGCG was similar to the phosphatidylinositol 3-kinase inhibitors wortmannin and LY-294002 to decrease protein kinase B (AKT) phosphorylation, cell number, and BrdU incorporation. These data imply that EGCG inhibits the growth of HVT through the ERK, p38, AMPK, and AKT pathways.
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan; and Taoyuan Armed Forces General Hospital, Longtan, Taoyuan, Taiwan.
authors.forename: Li-Jane
authors.initials: LJ
authors.lastname: Shih
authors.affiliation: Taoyuan Armed Forces General Hospital, Longtan, Taoyuan, Taiwan.
authors.forename: Tz-Fang
authors.initials: TF
authors.lastname: Chen
authors.affiliation: Taoyuan Armed Forces General Hospital, Longtan, Taoyuan, Taiwan.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Taoyuan Armed Forces General Hospital, Longtan, Taoyuan, Taiwan.
authors.forename: Hang-Shen
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan, Taiwan; and ykao@cc.ncu.edu.tw.
authors.forename: Yung-Hsi
authors.initials: YH
authors.lastname: Kao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000730:Androstadienes; D002867:Chromones; D009025:Morpholines; D013662:Tea; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D002392:Catechin; C045651:epigallocatechin gallate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D001973:Bromodeoxyuridine; D000077191:Wortmannin
keywords: AMP-activated protein kinase; epigallocatechin gallate; green tea; mitogen-activated protein kinase; trophoblast