Open Access<p>Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling</p>
Author(s) -
Xueping Liu,
Wei Chen,
QuanXing Liu,
JiGang Dai
Publication year - 2019
Publication title -
oncotargets and therapy
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.054
H-Index - 60
ISSN - 1178-6930
DOI - 10.2147/ott.s199161
Subject(s) - iκb kinase , apoptosis , chemistry , tumor necrosis factor alpha , cell cycle , kinase , cell growth , abietic acid , cell , flow cytometry , cancer research , nf κb , pharmacology , biochemistry , microbiology and biotechnology , biology , immunology , organic chemistry , resin acid , rosin
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.