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Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling.

ABSTRACT: 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.

SUBMITTER: Liu X

PROVIDER: S-EPMC6590626 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling.

Liu Xueping X Chen Wei W Liu Quanxing Q Dai Jigang J

OncoTargets and therapy 20190620

<b>Background:</b> 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. <b>Method:</b> 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. Finall ...[more]

PMID: 31354305

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Project description:Background: Targeting inflammatory microenvironment is a promising anti-tumor strategy. Paeonol is a phenolic compound with effective anti-inflammatory and anti-tumor properties. However, the effects of paeonol on non-small cell carcinoma (NSCLC) have not been fully investigated. Here, we evaluated the effects of paeonol on proliferation and metastasis of NSCLC and elucidated the underlying mechanisms. Methods: The effects of paeonol on inflammatory cytokines were determined by cell proliferation and ELISA assays. Assays of wound healing, single cell migration and perforation invasion were used to evaluate migration and invasion of NSCLC cells. Expression of marker proteins in epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family enzymes were detected by Western blot assays. Nude mouse A549 cells transplantation tumor model was used to study the anti-lung cancer effects of paeonol in vivo. TUNEL stanining were used to detect the apoptosis of tumor cells in A549 lung cancer mice, and Ki67 analysis was used to detect the proliferation of tumor cells in A549 lung cancer mice. Immunohistochemistry was used to detect the effects of paeonol on signaling molecules in tumor tissues. Results: Paeonol inhibited A549 cancer cell migration and invasion in vitro. Paeonol inhibited secreaion of inflammatory cytokines in A549 cells, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β. Paeonol altered the expression of marker proteins involved in EMT and MMP family enzymes. In addition, paeonol inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and phosphorylation of signal transducers and activators of transcription 3 (STAT3). Paeonol inhibited the growth of A549 cells transplanted tumors in nude mice. Conclusion: Paeonol potently inhibited NSCLC cell growth, migration and invasion associated with disruption of STAT3 and NF-κB pathways, suggesting that it could be a promising anti-metastatic candidate for tumor chemotherapy.

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Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling.

Publications

Abietic acid suppresses non-small-cell lung cancer cell growth via blocking IKKβ/NF-κB signaling.

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