title: MAPK inhibitors and siRNAs differentially affect cell death and ROS             levels in arsenic trioxide-treated human pulmonary fibroblast cells.
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.
authors.affiliation: Department of Physiology, Medical School, Research Institute for Endocrine Sciences Chonbuk National University, Jeonju 561-180, Republic of Korea. parkwh71@chonbuk.ac.kr
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D010087:Oxides / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D001152:Arsenicals; D010087:Oxides; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D000077237:Arsenic Trioxide