Exp Mol Med.  2011 Sep;43(9):494-500. 10.3858/emm.2011.43.9.056.

Continuous hypoxia attenuates paraquat-induced cytotoxicity in the human A549 lung carcinoma cell line

• Kim H
• Lee SW
• Baek KM
• Park JS
• Min JH

• KMID: 1022125
• DOI: http://doi.org/10.3858/emm.2011.43.9.056

Abstract

Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay, and by measuring lactate dehydrogenase (LDH) release. To elucidate the mechanism underlying this effect, we monitored the immunofluorescence of intracellular ROS and measured malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Continuous hypoxia protected the A549 cells from PQ-induced cytotoxicity. Continuous hypoxia for a period of 24 h significantly reduced intracellular ROS, decreased MDA concentration in the supernatant, and normalized SOD and GPx activities. Continuous hypoxia attenuated PQ-induced cell toxicity in A549 cells. This protective effect might be attributable to the suppression of PQ-induced ROS generation.

Keyword

cell death; hypoxia; oxidative stress; paraquat; reactive oxygen species

MeSH Terms

Apoptosis/drug effects
Cell Line, Tumor
Cell Proliferation/drug effects
Flavonoids/pharmacology
*Gene Expression Regulation, Neoplastic
Hepatocyte Growth Factor/*pharmacology
Humans
Inhibitor of Apoptosis Proteins/antagonists & inhibitors/*genetics
MAP Kinase Kinase Kinases/antagonists & inhibitors
Neoplasm Invasiveness
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-jun/genetics/*metabolism
Stomach Neoplasms/genetics/*metabolism/pathology
Urokinase-Type Plasminogen Activator/*genetics