MAPK inhibitors and siRNAs differentially affect cell death and ROS levels in arsenic trioxide-treated human pulmonary fibroblast cells

  • Authors:
    • Woo Hyun Park
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  • Published online on: January 27, 2012     https://doi.org/10.3892/or.2012.1661
  • Pages: 1611-1618
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Abstract

Arsenic trioxide (ATO; As2O3) induces cell death in various types of cancer cells including lung cancer via increasing reactive oxygen species (ROS) and regulating mitogen-activated protein kinase (MAPK) signaling cascades. However, little is known about the relationship between ATO and MAPK signaling in normal lung cells. Here, we investigated the effects of MAPK inhibitors and siRNAs on ATO-treated human pulmonary fibroblast (HPF) cells in relation to cell growth, cell death, ROS and glutathione (GSH) levels. ATO induced cell growth inhibition and death in HPF cells and it increased ROS levels including O2•- and GSH depleted cell number. None of the MAPK (MEK, JNK and p38) inhibitors affected cell growth inhibition and cell death by ATO. The MEK inhibitor decreased O2•- levels in ATO-treated HPF cells whereas JNK and p38 inhibitors generally increased ROS levels including O2•- in these cells. None of these inhibitors altered the ATO-induced GSH depletion. Moreover, ERK siRNA did not change HPF cell growth and death by ATO whereas JNK and p38 siRNAs enhanced cell growth inhibition and death. In addition, JNK and p38 siRNAs increased ROS levels and GSH depletion in ATO-treated HPF cells. In conclusion, MAPK inhibitors changed ROS levels in ATO-treated HPF cells, but did not affect cell growth inhibition and death. siRNAs targeting JNK and p38 showing an increase in ROS levels and GSH depletion in ATO-treated HPF cells augmented cell growth inhibition and death.

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May 2012
Volume 27 Issue 5

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

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Spandidos Publications style
Park WH: MAPK inhibitors and siRNAs differentially affect cell death and ROS levels in arsenic trioxide-treated human pulmonary fibroblast cells. Oncol Rep 27: 1611-1618, 2012
APA
Park, W.H. (2012). MAPK inhibitors and siRNAs differentially affect cell death and ROS levels in arsenic trioxide-treated human pulmonary fibroblast cells. Oncology Reports, 27, 1611-1618. https://doi.org/10.3892/or.2012.1661
MLA
Park, W. H."MAPK inhibitors and siRNAs differentially affect cell death and ROS levels in arsenic trioxide-treated human pulmonary fibroblast cells". Oncology Reports 27.5 (2012): 1611-1618.
Chicago
Park, W. H."MAPK inhibitors and siRNAs differentially affect cell death and ROS levels in arsenic trioxide-treated human pulmonary fibroblast cells". Oncology Reports 27, no. 5 (2012): 1611-1618. https://doi.org/10.3892/or.2012.1661