Anti-apoptotic effect of caspase inhibitors on H2O2-treated HeLa cells through early suppression of its oxidative stress

  • Authors:
    • Woo Hyun Park
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  • Published online on: March 12, 2014     https://doi.org/10.3892/or.2014.3084
  • Pages: 2413-2421
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Abstract

Oxidative stress-induced cytotoxicity in cervical cancer cells may be of toxicological interest. In the present study, the effects of exogenous H2O2 on cell growth and death in HeLa cervical cancer cells were investigated, and the anti-apoptotic effects of various caspase (pan-caspase, caspase-3, -8 or -9) inhibitors on H2O2-treated HeLa cells were also evaluated with regard to reactive oxygen species (ROS) and glutathione (GSH) levels. Based on MTT assays, H2O2 inhibited the growth of HeLa cells with an IC50 value of ~75 µM at 24 h. H2O2 increased the number of dead cells and Annexin V-FITC-positive cells in the HeLa cells, which was accompanied by the activation of caspase-3 and the loss of mitochondrial membrane potential (MMP; ΔΨm). However, relatively higher doses of H2O2 induced necrosis in HeLa cells. Caspase inhibitors significantly prevented H2O2-induced HeLa cell death. H2O2 increased ROS including O2•- at 24 h and increased the activity of catalase in HeLa cells. H2O2 also increased the ROS level at 1 h, and several caspase inhibitors attenuated the increased level at 1 h but not at 6, 12 and 24 h. H2O2 decreased the GSH level in HeLa cells at 1 h, and several caspase inhibitors attenuated the decreased level of GSH at this time. H2O2 induced GSH depletion at 24 h. In conclusion, H2O2 inhibited the growth of HeLa cells via apoptosis and/or necrosis, which was accompanied by intracellular increases in ROS levels and GSH depletion. Caspase inhibitors are suggested to suppress H2O2-induced oxidative stress to rescue HeLa cells at the early time point of 1 h.
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May-2014
Volume 31 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Park WH: Anti-apoptotic effect of caspase inhibitors on H2O2-treated HeLa cells through early suppression of its oxidative stress. Oncol Rep 31: 2413-2421, 2014.
APA
Park, W.H. (2014). Anti-apoptotic effect of caspase inhibitors on H2O2-treated HeLa cells through early suppression of its oxidative stress. Oncology Reports, 31, 2413-2421. https://doi.org/10.3892/or.2014.3084
MLA
Park, W. H."Anti-apoptotic effect of caspase inhibitors on H2O2-treated HeLa cells through early suppression of its oxidative stress". Oncology Reports 31.5 (2014): 2413-2421.
Chicago
Park, W. H."Anti-apoptotic effect of caspase inhibitors on H2O2-treated HeLa cells through early suppression of its oxidative stress". Oncology Reports 31, no. 5 (2014): 2413-2421. https://doi.org/10.3892/or.2014.3084