Green tea epigalocatechin gallate exhibits anticancer effect in human pancreatic carcinoma cells via inhibition of both FAK and IGF-1R

Abstract

Objectives: Green tea epigalocatechin galate (EGCG) has been shown to exhibit a growth-suppressive effect on human pancreatic cancer cells; however, the exact molecular mechanism by which EGCG suppresses cell proliferation is unclear. We hypothesize that interference with cell adhesion might be one mechanism. Methods: The effect of EGCG on cell adhesion and proliferation was examined using pancreatic cancer cells. Results: 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, when cultured at low density, can be significantly suppressed by EGCG treatment alone in a dose-dependent manner. At a dose of 100 μM that 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. Conclusions: Blocking FAK and IGF-1R by EGCG could prove valuable for targeted therapy, which can use in combination with other therapies, for pancreatic cancer. © Springer-Verlag 2010.