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Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade

  • Authors:
    • Xun Wang
    • Shuang Zou
    • Tong Ren
    • Li-Jun Zhao
    • Li-Fei Yu
    • Xiang-Yu Li
    • Xin Yan
    • Li-Jun Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The Third People's Hospital of Dalian, Non‑Directly Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116033, P.R. China, Department of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China, Department of Ophthalmology, The Third People's Hospital of Dalian, Non‑Directly Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116033, P.R. China, Department of Medical Oncology, The Third People's Hospital of Dalian, Non‑Directly Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116033, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 68
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    Published online on: March 1, 2021
       https://doi.org/10.3892/ijmm.2021.4901
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Abstract

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G‑actin/F‑actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)‑2/MMP‑9, caspase‑3/caspase‑9/poly(ADP‑ribose) polymerase (PARP)/cytochrome c, were determined by western blot analysis to assess the effects of targeting LIMK. The in vitro findings were verified in vivo by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G‑actin could be co‑transferred to the mitochondria to initiate the mitochondrial‑cytochrome c pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Zou S, Ren T, Zhao L, Yu L, Li X, Yan X and Zhang L: Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade. Int J Mol Med 47: 68, 2021.
APA
Wang, X., Zou, S., Ren, T., Zhao, L., Yu, L., Li, X. ... Zhang, L. (2021). Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade. International Journal of Molecular Medicine, 47, 68. https://doi.org/10.3892/ijmm.2021.4901
MLA
Wang, X., Zou, S., Ren, T., Zhao, L., Yu, L., Li, X., Yan, X., Zhang, L."Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade". International Journal of Molecular Medicine 47.5 (2021): 68.
Chicago
Wang, X., Zou, S., Ren, T., Zhao, L., Yu, L., Li, X., Yan, X., Zhang, L."Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade". International Journal of Molecular Medicine 47, no. 5 (2021): 68. https://doi.org/10.3892/ijmm.2021.4901
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Zou S, Ren T, Zhao L, Yu L, Li X, Yan X and Zhang L: Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade. Int J Mol Med 47: 68, 2021.
APA
Wang, X., Zou, S., Ren, T., Zhao, L., Yu, L., Li, X. ... Zhang, L. (2021). Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade. International Journal of Molecular Medicine, 47, 68. https://doi.org/10.3892/ijmm.2021.4901
MLA
Wang, X., Zou, S., Ren, T., Zhao, L., Yu, L., Li, X., Yan, X., Zhang, L."Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade". International Journal of Molecular Medicine 47.5 (2021): 68.
Chicago
Wang, X., Zou, S., Ren, T., Zhao, L., Yu, L., Li, X., Yan, X., Zhang, L."Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade". International Journal of Molecular Medicine 47, no. 5 (2021): 68. https://doi.org/10.3892/ijmm.2021.4901
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