title: 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.
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.
authors.affiliation: Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, Tokyo, Japan.
authors.forename: Hoang Anh
authors.initials: HA
authors.lastname: Vu
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Beppu
authors.forename: Hoang Thanh
authors.initials: HT
authors.lastname: Chi
authors.forename: Kousuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Phan Thi
authors.initials: PT
authors.lastname: Xinh
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanii
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohdomari
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013662:Tea
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D017526:Receptor, IGF Type 1; D051417:Focal Adhesion Kinase 1; D020928:Mitogen-Activated Protein Kinases