Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis

Atmospheric gas plasmas (AGPs) are able to selectively induce apoptosis in cancer cells, offering a promising alternative to conventional therapies that have unwanted side effects such as drug resistance and toxicity. However, the mechanism of AGP-induced cancer cell death is unknown. In this study,...

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Bibliographic Details
Published in:Molecular biology of the cell 2014-05, Vol.25 (9), p.1523-1531
Main Authors: Ishaq, Musarat, Kumar, Shailesh, Varinli, Hilal, Han, Zhao Jun, Rider, Amanda E, Evans, Margaret D M, Murphy, Anthony B, Ostrikov, Kostya
Format: Article
Language:English
Subjects:
Apoptosis
Atmosphere
Caspase 3 - metabolism
Caspase 7 - metabolism
Cell Line, Tumor
Cell Survival
Humans
MAP Kinase Kinase Kinase 5 - metabolism
Melanoma
Oxidative Stress
Plasma Gases - pharmacology
Reactive Oxygen Species - metabolism
Signal Transduction
Tumor Necrosis Factor-alpha - metabolism
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Summary:Atmospheric gas plasmas (AGPs) are able to selectively induce apoptosis in cancer cells, offering a promising alternative to conventional therapies that have unwanted side effects such as drug resistance and toxicity. However, the mechanism of AGP-induced cancer cell death is unknown. In this study, AGP is shown to up-regulate intracellular reactive oxygen species (ROS) levels and induce apoptosis in melanoma but not normal melanocyte cells. By screening genes involved in apoptosis, we identify tumor necrosis factor (TNF)-family members as the most differentially expressed cellular genes upon AGP treatment of melanoma cells. TNF receptor 1 (TNFR1) antagonist-neutralizing antibody specifically inhibits AGP-induced apoptosis signal, regulating apoptosis signal-regulating kinase 1 (ASK1) activity and subsequent ASK1-dependent apoptosis. Treatment of cells with intracellular ROS scavenger N-acetyl-l-cysteine also inhibits AGP-induced activation of ASK1, as well as apoptosis. Moreover, depletion of intracellular ASK1 reduces the level of AGP-induced oxidative stress and apoptosis. The evidence for TNF-signaling dependence of ASK1-mediated apoptosis suggests possible mechanisms for AGP activation and regulation of apoptosis-signaling pathways in tumor cells.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e13-10-0590