Epigallocatechin-3-gallate inhibits basic fibroblast growth factor-induced intracellular signaling transduction pathway in rat aortic smooth muscle cells.
Daily green tea drinking showed preventive effects on the progression of atherosclerosis. Although epigallocatechin-3-gallate [EGCG] has anti-proliferative effects on various cells, relatively little is known about the molecular mechanisms of the anti-proliferative effects of EGCG. To determine whether the transduction signals and protooncogene expression were affected by EGCG, this study investigated the molecular mechanism of the anti-proliferative effects in basic fibroblast growth factor (bFGF)-stimulated rat aortic smooth muscle cells (RAoSMCs). EGCG inhibited the proliferative response stimulated by 10% fetal bovine serum dose dependently in RAoSMCs (median inhibitory concentration [IC50]: 28.4 x 10(-6) M ). EGCG also inhibited the migration of bFGF-stimulated RAoSMCs in a dose-dependent manner, showing that 21.8 x 10(-6) M of EGCG significantly inhibited the migration by 75 +/- 5% in comparison with bFGF-stimulated migration. In RAoSMCs, EGCG dramatically inhibited Ras activation and c-jun N-terminal kinase (JNK) activity without affecting protein kinase C expression. Induction of c-jun mRNA stimulated by bFGF was significantly reduced dose dependently up to 87.3 x 10(-6) M of EGCG. These results indicate that the anti-proliferative effect of EGCG on RAoSMCs is partly Ras/JNK mediated, independent of protein kinase C, and is attributable to the downregulation of c-jun expression.
Hwang
Ki-Chul
KC
Cardiovascular Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul.
Lee
Kyung-Hye
KH
Jang
Yangsoo
Y
Yun
Yeo-Pyo
YP
Chung
Kwang-Hoe
KH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D002392:Catechin; C045651:epigallocatechin gallate; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins