MAPK inhibitors enhance cell death in pyrogallol-treated human pulmonary fibroblast cells via increasing O2•‑ levels

Han,Bo  Ram; Park,Woo  Hyun

doi:10.3892/ol.2017.6185

MAPK inhibitors enhance cell death in pyrogallol-treated human pulmonary fibroblast cells via increasing O2•‑ levels

Authors:
- Bo Ram Han
- Woo Hyun Park
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Affiliations: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju, Jeollabuk 54907, Republic of Korea
Published online on: May 17, 2017 https://doi.org/10.3892/ol.2017.6185
Pages: 1179-1185

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Abstract

Pyrogallol (PG) induces apoptosis in lung cancer cells via the overproduction of O2•‑ and affects mitogen‑activated protein kinases (MAPKs) in these cells. The aim of the present study was to elucidate the effect of PG and/or MAPK inhibitors on human pulmonary fibroblast (HPF) cell viability in relation to reactive oxygen species (ROS) and glutathione (GSH). Treatment with 50 or 100 µM PG inhibited the viability of HPF cells, and induced cell death and the loss of mitochondrial membrane potential (MMP; ΔΨm). In particular, treatment with 100 µM PG induced cell death via apoptosis as well as necrosis in HPF cells. PG increased mitochondrial O2•‑ levels and the number of GSH‑depleted HPF cells. All the MAPK (mitogen‑activated protein kinase kinase, c‑Jun N‑terminal kinase and p38) inhibitors enhanced the inhibition of cell viability, cell death and MMP (ΔΨm) loss in 100 µM PG‑treated HPF cells. All the inhibitors increased the O2•‑ levels in 100 µM PG‑treated HPF cells, but none of the inhibitors significantly altered the PG‑induced GSH depletion. In conclusion, PG treatment induced cell death via apoptosis and necrosis in HPF cells. Treatment with MAPK inhibitors slightly enhanced cell death in PG‑treated HPF cells. HPF cell death induced by PG and/or MAPK inhibitors was at least partially associated with changes in O2•‑ levels and GSH content. The present data provided useful information to understand PG‑induced normal lung cell death in association with MAPK signaling pathways and ROS levels.

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