Journal
ONCOLOGY REPORTS
Volume 28, Issue 2, Pages 749-757Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2012.1852
Keywords
arsenic trioxide; cell death; human pulmonary fibroblast; reactive oxygen species; glutathione
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Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2010-0007059]
- National Research Foundation of Korea [2010-0007059] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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; Delta Psi(m)). ATO increased ROS levels including O-2(center dot-) and GSH depleted cell numbers. NAC attenuated the growth inhibition, death and MMP (Delta Psi(m)) loss in ATO-treated HPF cells and also decreased the ROS levels in these cells. However, vitamin C enhanced the growth inhibition, death, MMP (Delta Psi(m),) loss and GSH depletion by ATO and even strongly increased mitochondrial O-2(-center dot) 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 (Delta Psi(m)) 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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