Apigenin Inhibits NNK-Induced Focal Adhesion Kinase Activation in Pancreatic Cancer Cells

作者：Hung Pham^*; Chen Monica; Takahashi Hiroki; King Jonathan; Reber Howard A; Hines Oscar Joe; Pandol Stephen; Eibl Guido

来源：Pancreas, 2012, 41(8): 1306-1315.

DOI：10.1097/MPA.0b013e31824d64d9

• Apigenin
• propranolol
• NNK
• FAK
• smoking
• pancreatic cancer

Objectives: Tobacco-derived carcinogen 4-(methylnitrosamino)-1( 3-pyridyl)-1-butanone (NNK) activates A-adrenergic receptor (A-AR) signaling through Src/focal adhesion kinases (FAKs)/mitogen-activated protein kinase to modulate proliferation, migration, and survival. Apigenin (4', 5, 7-trihydroxyflavone) is reported to attenuate proliferation and migration of cancer cells. This study was designed to determine the effects of apigenin on NNK-induced procarcinogenesis using human pancreatic cancer cells BxPC-3 and MIA PaCa-2, which express A-AR.
Methods: Proliferation and migration were assessed by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and scratch assays. A-AR, FAK/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) expression and activation were assessed by Western blotting and real-time polymerase chain reaction.
Results: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone caused a dose-and time-dependent increase in BxPC-3 and MIA PaCa-2 cell proliferation that was inhibited by propranolol or apigenin. 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone also stimulated a time-dependent increase in FAK and ERK activation that was suppressed by propranolol or apigenin. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanoneYenhanced gap closure at 24 hours was prevented by either propranolol or apigenin.
Conclusion: Apigenin suppressed the effects of NNK on pancreatic cancer cell proliferation and migration that are mediated through the A-AR and its downstream signals FAK and ERK activation. These findings suggest a therapeutic role for this natural phytochemical in attenuating the procarcinogenic effects of NNK on pancreatic cancer proliferation and migration.

• 出版日期2012-11