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PX‑12‑induced HeLa cell death is associated with oxidative stress and GSH depletion

  • Authors:
    • Hye Rim Shin
    • Bo Ra You
    • Woo Hyun Park

  • View Affiliations

  • Published online on: October 21, 2013     https://doi.org/10.3892/ol.2013.1637
  • Pages: 1804-1810
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Abstract

PX‑12, as an inhibitor of thioredoxin (Trx), has antitumor activity. However, little is known about the toxicological effect of PX‑12 on cervical cancer cells. In the present study, the growth inhibitory effects of PX‑12 on HeLa cervical cancer cells in association with reactive oxygen species (ROS) and glutathione (GSH) levels were investigated. Based on MTT assays, PX‑12 inhibited the growth of HeLa cells with an IC50 value of ~7 µM at 72 h. DNA flow cytometry analysis indicated that 5 and 10 µM PX‑12 significantly induced a G2/M phase arrest of the cell cycle. PX‑12 also increased the number of dead cells and annexin V‑fluorescein isothiocyanate‑positive cells, which was accompanied by the loss of mitochondrial membrane potential. All the investigated caspase inhibitors significantly rescued certain cells from PX‑12‑induced HeLa cell death. With respect to ROS and GSH levels, PX‑12 increased ROS levels (including O2•‑) in HeLa cells and induced GSH depletion. N‑acetyl cysteine markedly reduced the levels of O2•‑ in PX‑12‑treated HeLa cells, and prevented apoptotic cell death and GSH depletion in these cells. By contrast, L‑buthionine sulfoximine intensified cell death and GSH depletion in PX‑12‑treated HeLa cells. To conclude, this is the first study to demonstrate that PX‑12 inhibits the growth of HeLa cells via G2/M phase arrest, as well as inhibiting apoptosis; the effect was associated with intracellular increases in ROS levels and GSH depletion.
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December 2013
Volume 6 Issue 6

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

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  • Journal Metrics
  • Impact Factor: 2.5
  • Ranked Oncology
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  • CiteScore: 5.7
  • CiteScore Rank: Q2: #139/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.574
  • SCImago Journal Rank (SJR): 0.644
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Spandidos Publications style
Shin HR, You BR and Park WH: PX‑12‑induced HeLa cell death is associated with oxidative stress and GSH depletion. Oncol Lett 6: 1804-1810, 2013.
APA
Shin, H.R., You, B.R., & Park, W.H. (2013). PX‑12‑induced HeLa cell death is associated with oxidative stress and GSH depletion. Oncology Letters, 6, 1804-1810. https://doi.org/10.3892/ol.2013.1637
MLA
Shin, H. R., You, B. R., Park, W. H."PX‑12‑induced HeLa cell death is associated with oxidative stress and GSH depletion". Oncology Letters 6.6 (2013): 1804-1810.
Chicago
Shin, H. R., You, B. R., Park, W. H."PX‑12‑induced HeLa cell death is associated with oxidative stress and GSH depletion". Oncology Letters 6, no. 6 (2013): 1804-1810. https://doi.org/10.3892/ol.2013.1637