Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKK beta/NF-kappa B signaling

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-alpha induced phosphorylation of I kappa B kinase (IKK alpha/beta) (Ser176/180) and IkB alpha (Ser32), and inhibited the nuclear translocation of nuclear factor-kappa B. Moreover, we found that the activities of AA against NSCLC cells were mediated by its IKK beta inhibition. Molecular docking and MD simulations demonstrated that the mechanism of action between AA and IKK beta was through hydrophobic interactions. Conclusion: Our data indicate that AA could be a promising lead compound for the discovery of novel IKK beta inhibitors and potential agents for the treatment of NSCLC.