title: H₂O₂ inhibits the growth of human pulmonary fibroblast cells by inducing cell death, GSH depletion and G1 phase arrest.
abstract: Cultured normal human cells are invaluable biological models for mechanistic studies of oxidative stress. Exogenous hydrogen peroxide (H2O2) is often utilized as a representative model of an oxidative stressor. In the present study, the effect of exogenous H2O2 on cell growth and death was evaluated in normal human pulmonary fibroblast (HPF) cells with respect to reactive oxygen species (ROS) and glutathione (GSH) levels. In MTT assays, H2O2 inhibited the growth of HPF cells with an IC50 of ~50 µM at 24 h. DNA flow cytometric analysis indicated that 50-500 µM H2O2 significantly induced G1 phase arrest of the cell cycle. H2O2 induced cell death in the HPF cells, which was accompanied by cleavage of caspase-3 and loss of mitochondrial membrane potential (MMP; ∆ψm). However, H2O2 was not observed to significantly induce sub-G1 cells. H2O2 increased superoxide anion (O2‑) levels from 120 min and increases in ROS, including O2‑, were also detected at 24 h. H2O2 increased the activity of superoxide dismutase (SOD). H2O2 also induced GSH depletion in HPF cells at 24 h and decreased GSH levels after only 25 min. In conclusion, H2O2 inhibited the growth of HPF cells via apoptosis and/or necrosis as well as G1 phase arrest, which was accompanied by an intracellular increase in ROS levels and the depletion of GSH. The present study provides an important insight into the toxicological effects of exogenous H2O2 on normal HPF cells.
authors: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju 561‑180, Republic of Korea. parkwh71@chonbuk.ac.kr
authors: Woo Hyun
authors: WH
authors: Park
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008168:Lung / Q000166:cytology / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione