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Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage

  • Authors:
    • Gaoxiang Li
    • Yazhi Qian
    • Yuzhu Chen
    • Mingyue Cao
    • Xiaozhou Yang
    • Dexin Kong
    • Guiping Wang
    • Haiyan An
    • Nan Yang
    • Wei Huang
    • Yanyong Liu

  • View Affiliations

  • Published online on: November 29, 2022     https://doi.org/10.3892/ol.2022.13617
  • Article Number: 31

  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Numerous studies have shown that the release of stress hormones resulting from repeated exposure to chronic psychological stress increases DNA damage and promotes tumorigenesis. However, the mechanisms that enable cancerous cells adapt to stress hormone‑induced DNA damage and survive remain unclear. The present study aimed to investigate the impact of stress hormones on the survival of liver cancer cells and the underlying mechanism. HepG2 human liver cancer cells were treated with dexamethasone (DEX), epinephrine (EPI) and norepinephrine (NE) and subjected to the testing of DNA damage, cell survival and cell apoptosis by alkaline comet assay, CCK‑8 viability assay and flow cytometry, respectively. The protein expression levels of DNA damage response factors were determined by western blotting analysis. The results revealed that treatment of HepG2 cells with DEX, EPI and NE induced DNA damage without affecting cell survival or inducing apoptosis. The protein levels of wild‑type p53‑induced phosphatase 1 (Wip1), a type 2C family serine/threonine phosphatase, were increased, and the dephosphorylation of DNA damage response factors, including phosphorylated (p‑)ataxia‑telangiectasia mutated and p‑checkpoint kinase 2, occurred following treatment with DEX, EPI and NE. In addition, a cycloheximide chase assay was performed to explore the protein stability under treatment with stress hormones. Compared with vehicle‑treated cells, Wip1 exhibited increased protein stability in stress hormone‑treated HepG2 cells. Eventually, the depletion of Wip1 using small interfering RNA verified the role of Wip1 in the modulation of stress hormone‑induced DNA damage. These findings suggest that cancerous cells likely adapt to stress hormone‑induced DNA damage via Wip1 upregulation. The present study provides an insight into the underlying mechanism that links chronic psychological stress with tumor growth and progression.
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January-2023
Volume 25 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Li G, Qian Y, Chen Y, Cao M, Yang X, Kong D, Wang G, An H, Yang N, Huang W, Huang W, et al: Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage. Oncol Lett 25: 31, 2023.
APA
Li, G., Qian, Y., Chen, Y., Cao, M., Yang, X., Kong, D. ... Liu, Y. (2023). Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage. Oncology Letters, 25, 31. https://doi.org/10.3892/ol.2022.13617
MLA
Li, G., Qian, Y., Chen, Y., Cao, M., Yang, X., Kong, D., Wang, G., An, H., Yang, N., Huang, W., Liu, Y."Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage". Oncology Letters 25.1 (2023): 31.
Chicago
Li, G., Qian, Y., Chen, Y., Cao, M., Yang, X., Kong, D., Wang, G., An, H., Yang, N., Huang, W., Liu, Y."Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage". Oncology Letters 25, no. 1 (2023): 31. https://doi.org/10.3892/ol.2022.13617