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Title 

An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib

Authors 

Taeho KwonJ K RhoJ C LeeYoung Ho ParkHye-Jun ShinSunhwa ChoYong-Kook KangBo Yeon KimD Y YoonDae Yeul Yu

Publisher 

Korean Society of Medical Biochemistry

Issue Date 

2015

Citation 

Experimental and Molecular Medicine, vol. 47, no. 0, pp. e165-e165

Abstract 

Redox adaptation is an important concept that explains the mechanisms by which cancer cells survive under persistent endogenous oxidative stress and become resistant to certain anticancer agents. To investigate this concept, we determined the expression levels of peroxiredoxins (Prxs), antioxidant enzymes in drug-resistant non-small cell lung carcinoma cells. Prx II was remarkably increased only in A549/GR (gefitinib-resistant) cells compared with A549 cells, consistent with methylation/demethylation. Prx II was highly methylated in the A549 cells but was demethylated in the A549/GR cells. The elevated expression of Prx II resulted in the downregulation of reactive oxygen species (ROS) and cell death and upregulation of cell cycle progression in the A549/GR cells. When Prx II mRNA in the A549/GR cells was knocked down, the levels of ROS and apoptosis were significantly recovered to the levels of the controls. In addition, signaling molecules involved in apoptosis were increased in the A549/GR-shPrx II cells. There was no difference in the expression of MAPK/ERK between the A549/GR cells and A549/GRshPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GRshPrx II cells. Colony number and tumor growth were significantly decreased in the A549/GR-shPrx II cells compared with the A549/GR cells. Our findings suggest that Prx II has an important role in cancer cell survival via the modulation of signaling molecules involved in apoptosis and the phosphorylation of JNK by the downregulation of ROS levels in A549/GR cells.

ISSN 

1226-3613

Link 

http://dx.doi.org/10.1038/emm.2015.24

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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