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Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB 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 grow...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590626/ https://www.ncbi.nlm.nih.gov/pubmed/31354305 http://dx.doi.org/10.2147/OTT.S199161 |
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author | Liu, Xueping Chen, Wei Liu, Quanxing Dai, Jigang |
author_facet | Liu, Xueping Chen, Wei Liu, Quanxing Dai, Jigang |
author_sort | Liu, Xueping |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6590626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-65906262019-07-26 Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling Liu, Xueping Chen, Wei Liu, Quanxing Dai, Jigang Onco Targets Ther Original Research 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. Dove 2019-06-20 /pmc/articles/PMC6590626/ /pubmed/31354305 http://dx.doi.org/10.2147/OTT.S199161 Text en © 2019 Liu et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Liu, Xueping Chen, Wei Liu, Quanxing Dai, Jigang Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling |
title | Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling |
title_full | Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling |
title_fullStr | Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling |
title_full_unstemmed | Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling |
title_short | Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling |
title_sort | abietic acid suppresses non-small-cell lung cancer cell growth via blocking ikkβ/nf-κb signaling |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590626/ https://www.ncbi.nlm.nih.gov/pubmed/31354305 http://dx.doi.org/10.2147/OTT.S199161 |
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