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

Ishaq, Musarat, Kumar, Shailesh, Varinli, Hilal, Han, Zhao Jun, Rider, Amanda E., Evans, Margaret D.M., Murphy, Anthony B., & Ostrikov, Kostya (2014) Atmospheric gas plasma–induced ROS production activates TNF-ASK1 pathway for the induction of melanoma cancer cell apoptosis. Molecular Biology of the Cell, 25(9), pp. 1523-1531.

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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.

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46 citations in Web of Science®
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ID Code: 73506
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 2 months
DOI: 10.1091/mbc.E13-10-0590
ISSN: 1939-4586
Divisions: Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 08 Jul 2014 05:19
Last Modified: 21 Jun 2017 21:01

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