IκB激酶
细胞凋亡
化学
肿瘤坏死因子α
细胞周期
激酶
细胞生长
枞酸
细胞
流式细胞术
癌症研究
NF-κB
药理学
生物化学
分子生物学
生物
免疫学
有机化学
树脂酸
松香
作者
Xueping Liu,Wei Chen,Quan‐Xing Liu,Ji‐Gang Dai
摘要
Background: Abietic acid (AA) is one of the terpenoids, which are multifunctional natural compounds.It has been reported that AA possesses favorable therapeutic effects on inflammation and obesity.Method: In the present study, we determined the inhibitory effect of AA on the proliferation and growth of non-small-cell lung cancer (NSCLC) cell lines for the first time.Then, flow cytometry and Western blot analysis were applied to determine the cell apoptosis and cell cycle.Finally, surface plasmon resonance, molecular docking and molecular dynamics (MD) simulation were performed to explore the underlying molecular mechanisms.Results: In vitro experiments indicated that AA displays significant anti-proliferative, cell cycle arresting and pro-apoptotic activities.Mechanistically, AA abrogated tumor necrosis factor-α induced phosphorylation of IκB kinase (IKKα/β) (Ser176/180) and IkBα (Ser32), and inhibited the nuclear translocation of nuclear factor-κB.Moreover, we found that the activities of AA against NSCLC cells were mediated by its IKKβ inhibition.Molecular docking and MD simulations demonstrated that the mechanism of action between AA and IKKβ was through hydrophobic interactions.Conclusion: Our data indicate that AA could be a promising lead compound for the discovery of novel IKKβ inhibitors and potential agents for the treatment of NSCLC.
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