Green tea epigallocatechin gallate exhibits anticancer effect in human pancreatic carcinoma cells via the inhibition of both focal adhesion kinase and insulin-like growth factor-I receptor

J Biomed Biotechnol. 2010:2010:290516. doi: 10.1155/2010/290516. Epub 2011 Jan 26.

Abstract

The exact molecular mechanism by which epigallocatechin gallate (EGCG) suppresses human pancreatic cancer cell proliferation is unclear. We show here that EGCG-treated pancreatic cancer cells AsPC-1 and BxPC-3 decrease cell adhesion ability on micro-pattern dots, accompanied by dephosphorylations of both focal adhesion kinase (FAK) and insulin-like growth factor-1 receptor (IGF-1R) whereas retained the activations of mitogen-activated protein kinase and mammalian target of rapamycin. The growth of AsPC-1 and BxPC-3 cells can be significantly suppressed by EGCG treatment alone in a dose-dependent manner. At a dose of 100 μM which completely abolishes activations of FAK and IGF-1R, EGCG suppresses more than 50% of cell proliferation without evidence of apoptosis analyzed by PARP cleavage. Finally, the MEK1/2 inhibitor U0126 enhances growth-suppressive effect of EGCG. Our data suggests that blocking FAK and IGF-1R by EGCG could prove valuable for targeted therapy, which can be used in combination with other therapies, for pancreatic cancer.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Apoptosis / physiology
  • Catechin / analogs & derivatives*
  • Catechin / metabolism
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Focal Adhesion Kinase 1 / antagonists & inhibitors*
  • Humans
  • Mitogen-Activated Protein Kinases / metabolism
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Tea*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Tea
  • Catechin
  • epigallocatechin gallate
  • Receptor, IGF Type 1
  • Focal Adhesion Kinase 1
  • Mitogen-Activated Protein Kinases