title: An important role for peroxiredoxin II in survival of A549 lung cancer cells resistant to gefitinib.
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/GR-shPrx II cells, but the phosphorylation of JNK was increased in the A549/GR cells and was markedly decreased in the A549/GR-shPrx 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.
authors.affiliation: 1] Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea [2] Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Taeho
authors.initials: T
authors.lastname: Kwon
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Rho
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Park
authors.affiliation: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Hye-Jun
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Sunwha
authors.initials: S
authors.lastname: Cho
authors.affiliation: Development and Differentiation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Yong-Kook
authors.initials: YK
authors.lastname: Kang
authors.affiliation: World Class Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungbuk, Korea.
authors.forename: Bo-Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.affiliation: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018384:Oxidative Stress / Q000187:drug effects; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; D000077156:Gefitinib