title: Atmospheric gas plasma-induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis.
abstract: 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.
authors.affiliation: CSIRO Materials Science and Engineering, North Ryde, NSW 1670, Australia Plasma Nanoscience Center, CSIRO Materials Science and Engineering, Lindfield, NSW 2070, Australia CSIRO Animal, Food and Health Sciences, North Ryde, NSW 1670, Australia School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane, QLD 4000, Australia.
authors.forename: Musarat
authors.initials: M
authors.lastname: Ishaq
authors.forename: Shailesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Hilal
authors.initials: H
authors.lastname: Varinli
authors.forename: Zhao Jun
authors.initials: ZJ
authors.lastname: Han
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Rider
authors.forename: Margaret D M
authors.initials: MD
authors.lastname: Evans
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Murphy
authors.forename: Kostya
authors.initials: K
authors.lastname: Ostrikov
mesh_terms: D017209:Apoptosis; D001272:Atmosphere; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D008545:Melanoma; D018384:Oxidative Stress; D058626:Plasma Gases / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D058626:Plasma Gases; D017382:Reactive Oxygen Species; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7