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Article

Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion

  • Authors:
    • Bo Ra You
    • Woo Hyun Park
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea
  • Pages: 749-757
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    Published online on: June 6, 2012
       https://doi.org/10.3892/or.2012.1852
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Abstract

Arsenic trioxide (ATO; As2O3) induces apoptotic cell death in various cancer cells including lung cancer via the induction of reactive oxygen species (ROS). However, little is known about the toxicological effects of ATO on normal primary lung cells. Here, we investigated the effects of N-acetyl cysteine (NAC) and vitamin C (well-known antioxidants) or L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) on ATO-treated human pulmonary fibroblast (HPF) cells in relation to cell death, ROS and glutathione (GSH). ATO induced growth inhibition and death in HPF cells, accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). ATO increased ROS levels including O2•- and GSH depleted cell numbers. NAC attenuated the growth inhibition, death and MMP (∆ψm) loss in ATO-treated HPF cells and also decreased the ROS levels in these cells. However, vitamin C enhanced the growth inhibition, death, MMP (∆ψm) loss and GSH depletion by ATO and even strongly increased mitochondrial O2•- levels in ATO-treated HPF cells. BSO showed a strong increase in ROS levels in ATO-treated HPF cells and intensified the growth inhibition, cell death, MMP (∆ψm) loss and GSH depletion. Moreover, superoxide dismutase (SOD2) or thioredoxin (TXN) siRNAs attenuated HPF cell death by ATO, which was not correlated with ROS and GSH level changes. In conclusion, ATO induced the growth inhibition and death of HPF cells, accompanied by increasing ROS levels and GSH depletion. NAC attenuated HPF cell death by ATO whereas vitamin C and BSO enhanced the death.
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Copy and paste a formatted citation
Spandidos Publications style
You BR and Park WH: Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol Rep 28: 749-757, 2012.
APA
You, B.R., & Park, W.H. (2012). Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncology Reports, 28, 749-757. https://doi.org/10.3892/or.2012.1852
MLA
You, B. R., Park, W. H."Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 28.2 (2012): 749-757.
Chicago
You, B. R., Park, W. H."Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 28, no. 2 (2012): 749-757. https://doi.org/10.3892/or.2012.1852
Copy and paste a formatted citation
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Spandidos Publications style
You BR and Park WH: Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol Rep 28: 749-757, 2012.
APA
You, B.R., & Park, W.H. (2012). Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncology Reports, 28, 749-757. https://doi.org/10.3892/or.2012.1852
MLA
You, B. R., Park, W. H."Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 28.2 (2012): 749-757.
Chicago
You, B. R., Park, W. H."Arsenic trioxide induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 28, no. 2 (2012): 749-757. https://doi.org/10.3892/or.2012.1852
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