Apigenin inhibits NNK-induced focal adhesion kinase activation in pancreatic cancer cells.
Apigenin inhibits NNK-induced focal adhesion kinase activation in pancreatic cancer cells.
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DOI：
10.1097/mpa.0b013e31824d64d9
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发表时间：
2012-11
期刊：
影响因子：
2.9
通讯作者：
Eibl G
中科院分区：
文献类型：
--
作者：
Pham H;Chen M;Takahashi H;King J;Reber HA;Hines OJ;Pandol S;Eibl G
Tobacco-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NNK, activates β-adrenergic receptor (β-AR) signaling through Src/focal adhesion kinases (FAK)/MAPK 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 pro-carcinogenesis using human pancreatic cancer cells BxPC-3 and MIA PaCa-2 that express β-AR. Proliferation and migration were assessed by standard MTT and scratch assays. β-AR, FAK/MAPK and ERK expression and activation were assessed by Western blotting and real time PCR. NNK caused a dose- and time-dependent increase in BxPC-3 and MIA PaCa-2 cell proliferation that was inhibited by propranolol or apigenin. NNK also stimulated a time-dependent increase in FAK and ERK activation that was suppressed by propranolol or apigenin. NNK-enhanced gap closure at 24 hr was prevented by either propranolol or apigenin. Apigenin suppressed the effects of NNK on pancreatic cancer cell proliferation and migration that are mediated through the β-AR and its downstream signals FAK and ERK activation. These findings suggest a therapeutic role for this natural phytochemical in attenuating the pro-carcinogenic effects of NNK on pancreatic cancer proliferation and migration.
