title: Luteolin exerts pro-apoptotic effect and anti-migration effects on A549 lung adenocarcinoma cells through the activation of MEK/ERK signaling pathway.
abstract: An increasing amount of evidence suggests that luteolin, a common dietary flavonoid that is widely distributed in plants and foods, has been shown to be protective against cancer. However, the precise underlying mechanisms of its action against lung cancer are still poorly understood. In the present study, we investigated whether luteolin exhibits the anti-cancer effect in lung cancer through the induction of cell apoptosis and inhibition of cell migration, and whether mitogen-activated protein kinases (MAPKs) and Akt signaling pathways are required. Results revealed that luteolin exerted an anti-proliferation effect in a dose- and time-dependent manner in A549 lung adenocarcinoma cells, and induced apoptosis with a concomitant increase in the activation of caspases-3 and -9, diminution of Bcl-2, elevation in Bax expression, and the phosphorylation of MEK and its down-stream kinase ERK, as well as the activation of Akt. Luteolin also dramatically inhibited cell motility and migration in A549 cells. The inhibitor of MEK-ERK pathway protected against luteolin-induced cell death and suppressed the apoptosis-inducing and anti-migratory effects of luteolin, suggesting MEK-ERK signaling pathway plays an important role in mediating the pro-apoptotic effect and anti-migration effects of luteolin. Taken together, this study provides a new insight into the mode of action of luteolin on lung cancer.
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, China; Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Guanmin
authors.initials: G
authors.lastname: Meng
authors.affiliation: Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, China.
authors.forename: Kequn
authors.initials: K
authors.lastname: Chai
authors.affiliation: Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Xinda
authors.initials: X
authors.lastname: Li
authors.affiliation: Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China. Electronic address: hzhwh@126.com.
authors.forename: Weihua
authors.initials: W
authors.lastname: Huang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D047311:Luteolin / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D051057:Proto-Oncogene Proteins c-akt; D047311:Luteolin
keywords: Apoptosis; Caspase; Lung cancer; Luteolin; MEK/ERK signaling; Migration