title: NOX5-L can stimulate proliferation and apoptosis depending on its levels and cellular context, determining cancer cell susceptibility to cisplatin.
abstract: The NADPH oxidase, NOX5, is known to stimulate cell proliferation in some cancers by generating reactive oxygen species (ROS). We show here that the long form of NOX5 (NOX5-L) also promotes cell death, and thus determines the balance of proliferation and death, in skin, breast and lung cancer cells. Moderate expression of NOX5-L induced cell proliferation accompanied by AKT and ERK phosphorylation, whereas an increase in NOX5-L above a certain threshold promoted cancer cell death accompanied by caspase-3 activation. Notably, cisplatin treatment increased NOX5-L levels through CREB activation and enhanced NOX5-L activity through augmentation of Ca2+ release and c-Abl expression, ultimately triggering ROS-mediated cancer cell death-a distinct pathway absent in normal cells. These results indicate that NOX5-L determines cellular responses in a concentration- and context-dependent manner.
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.|Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Dho
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Eun-Soo
authors.initials: ES
authors.lastname: Kwon
authors.affiliation: Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305-353, Republic of Korea.
authors.forename: Jae Cheong
authors.initials: JC
authors.lastname: Lim
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Sung Sup
authors.initials: SS
authors.lastname: Park
authors.affiliation: Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.|Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305-333, Republic of Korea.
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kwon
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D000074664:NADPH Oxidase 5; D019255:NADPH Oxidases; C431571:NOX5 protein, human; D002945:Cisplatin
keywords: CREB; NOX5-L; ROS; c-Abl; cisplatin