Research Papers:

NOX5-L can stimulate proliferation and apoptosis depending on its levels and cellular context, determining cancer cell susceptibility to cisplatin

So Hee Dho _, Ji Young Kim, Eun-Soo Kwon, Jae Cheong Lim, Sung Sup Park and Ki-Sun Kwon

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Oncotarget. 2015; 6:39235-39246. https://doi.org/10.18632/oncotarget.5743

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So Hee Dho1,2,*, Ji Young Kim1,*, Eun-Soo Kwon1, Jae Cheong Lim2, Sung Sup Park1, Ki-Sun Kwon1,3

1Aging Research Institute, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305–806, Republic of Korea

2Radioisotope Research Division, Department of Research Reactor Utilization, Korea Atomic Energy Research Institute, Daejeon 305–353, Republic of Korea

3Department of Functional Genomics, University of Science and Technology (UST), Daejeon 305–333, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Ki-Sun Kwon, e-mail: kwonks@kribb.re.kr

Keywords: c-Abl, CREB, cisplatin, NOX5-L, ROS

Received: June 25, 2015     Accepted: October 05, 2015     Published: October 15, 2015


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.

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