Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2005; 11(22): 3368-3374
Published online Jun 14, 2005. doi: 10.3748/wjg.v11.i22.3368
Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation and migration of rat pancreatic stellate cells
Atsushi Masamune, Kazuhiro Kikuta, Masahiro Satoh, Noriaki Suzuki, Tooru Shimosegawa
Atsushi Masamune, Kazuhiro Kikuta, Masahiro Satoh, Noriaki Suzuki, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Author contributions: All authors contributed equally to the work.
Supported by the Grant-in-Aid for Encouragement of Young Scientists from Japan Society for the Promotion of Science, No. 16590572, Pancreas Research Foundation of Japan, No. 01-01, and the Kanae Foundation for Life and Socio-Medical Science
Correspondence to: Dr. Atsushi Masamune, 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
Telephone: +81-22-717-7171 Fax: +81-22-717-7177
Received: October 14, 2004
Revised: October 15, 2004
Accepted: November 19, 2004
Published online: June 14, 2005
Abstract

AIM: 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 β-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 β-receptor and downstream activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways.

CONCLUSION: EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs through the inhibition of PDGF-mediated signaling pathways.

Keywords: Pancreatitis; Pancreatic fibrosis; Pancreatic stellate cells; Epigallocatechin-3-gallate; Green tea; Platelet-derived growth factor; Proliferation; Migration