Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation and migration of rat pancreatic stellate cells.
OBJECTIVE
To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of pancreatic stellate cells (PSCs).


METHODS
PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Cell migration was assessed using modified Boyden chambers. Cyclin D1, p21Waf1, and p27Kip1 expression and phosphorylation of PDGF beta-receptor, extracellular signal-regulated kinase, and Akt were examined by Western blotting. Activation of phospha-tidylinositol 3-kinase was examined by kinase assay using phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry after staining with propidium iodide.


RESULTS
EGCG at non-cytotoxic concentrations inhibited PDGF-induced proliferation and migration. This effect was associated with the inhibition of cell cycle progression beyond the G1 phase, decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine phosphorylation of PDGF beta-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways.


CONCLUSIONS
EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibition of PDGF-mediated signaling pathways.
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cyo, Aoba-ku, Sendai 980-8574, Japan. amasamune@int3.med.tohoku.ac.jp
Kikuta
Kazuhiro
K
Satoh
Masahiro
M
Suzuki
Noriaki
N
Shimosegawa
Tooru
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004347:Drug Interactions; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D010636:Phenols; D010982:Platelet-Derived Growth Factor; D059808:Polyphenols; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate