title: Green tea (-)-epigallocatechin gallate induced growth inhibition of human placental choriocarcinoma cells.
abstract: This study investigated the pathways involved in the effect of green tea epigallocatechin gallate (EGCG) on mitogenesis in BeWo, JEG-3, and JAR placental choriocarcinoma cells. EGCG inhibited cell proliferation in dose-dependent and time-dependent manners, as indicated by the number of cells and incorporation of bromodeoxyuridine (BrdU). A catechin-specific effect of green tea was evident; EGCG was more effective than epicatechin, epicatechin gallate, and epigallocatechin in suppressing cell growth. When all three of the mitogen-activated protein kinase (MAPK) subfamilies, i.e., ERK, p38, and JNK, were examined, EGCG significantly increased levels of phospho-ERK1/2 (pERK1/2) and phospho-p38 (pp38) and did not alter the total protein levels of ERK1/2, p38 MAPK, JNK, and phospho-JNK. EGCG-induced increases in the levels of pERK1/2 and pp38 proteins were prevented by pre-treatment with specific inhibitors of ERK1/2 MAPK and p38 MAPK, respectively. These inhibitors also suppressed EGCG-induced decreases in both cell number and BrdU incorporation. Moreover, pre-treatment with an AMP-activated protein kinase (AMPK) inhibitor prevented the actions of EGCG on proliferation and AMPK phosphorylation. These data suggest that EGCG mediates choriocarcinoma cell growth via the AMPK, ERK, and p38 pathways, but not JNK pathway.
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan 320, Taiwan; Taoyuan Armed Forces General Hospital, Longtan, Taoyuan 325, Taiwan.
authors.forename: Li-Jane
authors.initials: LJ
authors.lastname: Shih
authors.affiliation: Taoyuan Armed Forces General Hospital, Longtan, Taoyuan 325, Taiwan.
authors.forename: Yu-Ren
authors.initials: YR
authors.lastname: Lin
authors.affiliation: Taoyuan Armed Forces General Hospital, Longtan, Taoyuan 325, Taiwan.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Taoyuan Armed Forces General Hospital, Longtan, Taoyuan 325, Taiwan.
authors.forename: Hang-Shen
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Life Sciences, National Central University, Jhongli, Taoyuan 320, Taiwan. Electronic address: ykao@cc.ncu.edu.tw.
authors.forename: Yung-Hsi
authors.initials: YH
authors.lastname: Kao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D050256:Antimitotic Agents; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D002822:Choriocarcinoma / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D011247:Pregnancy; D013662:Tea; D014594:Uterine Neoplasms / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D050256:Antimitotic Agents; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Choriocarcinoma cell; Epigallocatechin gallate; Green tea; Mitogen-activated protein kinase; Placenta