TY - JOUR
T1 - Green tea (–)-epigallocatechin gallate inhibits the growth of human villous trophoblasts via the ERK, p38, AMP-activated protein kinase, and protein kinase B pathways
AU - Shih, Li Jane
AU - Chen, Tz Fang
AU - Lin, Cheng Kuo
AU - Liu, Hang Shen
AU - Kao, Yung Hsi
N1 - Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - AMP-activated protein kinase
KW - Epigallocatechin gallate
KW - Green tea
KW - Mitogen-activated protein kinase
KW - Trophoblast
UR - http://www.scopus.com/inward/record.url?scp=84983656453&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.00003.2016
DO - 10.1152/ajpcell.00003.2016
M3 - 期刊論文
C2 - 27147558
AN - SCOPUS:84983656453
SN - 0363-6143
VL - 311
SP - C308-C321
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 2
ER -