AMP-activated protein kinase (AMPK) activation is involved in chrysin-induced growth inhibition and apoptosis in cultured A549 lung cancer cells.
Here we show that chrysin induces growth inhibition and apoptosis in cultured lung cancer A549 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to this process. Our Western-blots results demonstrated a significant AMPK activation after chrysin treatment in A549 cells. Inhibition of AMPK by shRNA-mediated gene silencing, or by its inhibitor, diminished chrysin-induced A549 cell growth inhibition and apoptosis. Forced activation of AMPK by introducing a constitutively active form of AMPKα (CA-AMPKα), or by its activators, mimicked chrysin's effect. For mechanism analysis, we found chrysin inhibited Akt/mammalian target of rapamycin (mTOR) activation, and knocking-down of AMPK by shRNA almost reversed this effect. Finally, we observed that a relative low dose of chrysin enhanced doxorubicin-induced AMPK activation to promote A549 cell apoptosis. Our study suggests that activation of AMPK by chrysin contributes to Akt suppression, growth inhibition and apoptosis in human lung cancer cells, and agents that could activate AMPK may serve as useful adjuvants for traditional chemotherapy against lung cancer.
Department of Cardiothoracic Surgery, Nanjing Hospital affiliated to Nanjing Medical University, 68 Chang-le Road, Qin-huai District, Nanjing, Jiangsu 210006, China. shaojunjie7@hotmail.com
Jun-jie
JJ
Shao
Ai-ping
AP
Zhang
Wei
W
Qin
Lin
L
Zheng
Yi-fan
YF
Zhu
Xin
X
Chen
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D004317:Doxorubicin / Q000494:pharmacology; D004789:Enzyme Activation; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D005419:Flavonoids; C043561:chrysin; D004317:Doxorubicin; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases