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Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway

  • Authors:
    • Fenglin Zhang
    • Yan Qi
    • Jing Li
    • Boyang Liu
    • Zhonghui Liu
    • Xueling Cui
  • View Affiliations / Copyright

    Affiliations: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Key Laboratory of Neuroimmunology and Clinical Immunology in Jilin, Changchun, Jilin 130021, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 29
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    Published online on: December 20, 2023
       https://doi.org/10.3892/or.2023.8688
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Abstract

Activin A, a member of the transforming growth factor‑β (TGF‑β) superfamily, has been implicated in the tumorigenesis and progression of various cancers. However, it remains unclear whether activin A induces apoptosis in human lung adenocarcinoma cells through the endoplasmic reticulum (ER) stress pathway. In the present study, BrdU, flow cytometry and western blotting were used to examine cell proliferation, apoptosis and protein expression, respectively. The present study revealed that activin A inhibited human lung adenocarcinoma A549 cell proliferation, induced apoptosis, and upregulated the protein levels of C/EBP homologous protein (CHOP), growth arrest and DNA damage‑inducible protein 34 (GADD34), cleaved‑caspase‑3 and caspase‑12. Furthermore, the administration of activin A did not alter the levels of suppressor of mothers against decapentaplegic 3 (Smad3) or phosphorylated (p)‑Smad3 proteins, whereas, it significantly elevated the levels of ActRIIA and p‑extracellular signal regulated kinase proteins 1 and 2 (ERK1/2) proteins in A549 cells. The apoptotic effects of activin A on A549 cells were attenuated by the ERK inhibitor FR180204, which also downregulated CHOP and caspase‑12 protein levels. Additionally, activin A increased intracellular calcium flux in A549 cells, and the calcium ion chelator BAPTA acetoxymethyl ester (BAPTA‑AM) inhibited activin A‑induced A549 cell apoptosis, whereas the calcium agonist ionomycin significantly increased apoptosis of A549 cells induced by activin A. These findings indicated that the activation of the ER stress pathway resulting in apoptosis of A549 cells triggered by activin A is facilitated by the ActRIIA‑ERK1/2 signaling and calcium signaling. The present findings suggest that the agonists of ERK and calcium signaling exhibit promising clinical therapeutic potential for the induction of apoptosis in lung adenocarcinoma.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang F, Qi Y, Li J, Liu B, Liu Z and Cui X: Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway. Oncol Rep 51: 29, 2024.
APA
Zhang, F., Qi, Y., Li, J., Liu, B., Liu, Z., & Cui, X. (2024). Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway. Oncology Reports, 51, 29. https://doi.org/10.3892/or.2023.8688
MLA
Zhang, F., Qi, Y., Li, J., Liu, B., Liu, Z., Cui, X."Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway". Oncology Reports 51.2 (2024): 29.
Chicago
Zhang, F., Qi, Y., Li, J., Liu, B., Liu, Z., Cui, X."Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway". Oncology Reports 51, no. 2 (2024): 29. https://doi.org/10.3892/or.2023.8688
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang F, Qi Y, Li J, Liu B, Liu Z and Cui X: Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway. Oncol Rep 51: 29, 2024.
APA
Zhang, F., Qi, Y., Li, J., Liu, B., Liu, Z., & Cui, X. (2024). Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway. Oncology Reports, 51, 29. https://doi.org/10.3892/or.2023.8688
MLA
Zhang, F., Qi, Y., Li, J., Liu, B., Liu, Z., Cui, X."Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway". Oncology Reports 51.2 (2024): 29.
Chicago
Zhang, F., Qi, Y., Li, J., Liu, B., Liu, Z., Cui, X."Activin A induces apoptosis of human lung adenocarcinoma A549 cells through endoplasmic reticulum stress pathway". Oncology Reports 51, no. 2 (2024): 29. https://doi.org/10.3892/or.2023.8688
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