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Tumor-selective mitochondrial network collapse induced by atmospheric gas plasma-activated medium.
- Source :
-
Oncotarget [Oncotarget] 2016 Apr 12; Vol. 7 (15), pp. 19910-27. - Publication Year :
- 2016
-
Abstract
- Non-thermal atmospheric gas plasma (AGP) exhibits cytotoxicity against malignant cells with minimal cytotoxicity toward normal cells. However, the mechanisms of its tumor-selective cytotoxicity remain unclear. Here we report that AGP-activated medium increases caspase-independent cell death and mitochondrial network collapse in a panel of human cancer cells, but not in non-transformed cells. AGP irradiation stimulated reactive oxygen species (ROS) generation in AGP-activated medium, and in turn the resulting stable ROS, most likely hydrogen peroxide (H2O2), activated intracellular ROS generation and mitochondrial ROS (mROS) accumulation. Culture in AGP-activated medium resulted in cell death and excessive mitochondrial fragmentation and clustering, and these responses were inhibited by ROS scavengers. AGP-activated medium also increased dynamin-related protein 1-dependent mitochondrial fission in a tumor-specific manner, and H2O2 administration showed similar effects. Moreover, the vulnerability of tumor cells to mitochondrial network collapse appeared to result from their higher sensitivity to mROS accumulation induced by AGP-activated medium or H2O2. The present findings expand our previous observations on death receptor-mediated tumor-selective cell killing and reinforce the importance of mitochondrial network remodeling as a powerful target for tumor-selective cancer treatment.
- Subjects :
- Apoptosis drug effects
Cell Proliferation drug effects
Cells, Cultured
Humans
Hydrogen Peroxide pharmacology
Melanocytes cytology
Melanocytes drug effects
Melanocytes metabolism
Mitochondria drug effects
Mitochondria metabolism
Neoplasms drug therapy
Neoplasms metabolism
Oxidants pharmacology
Oxidative Stress drug effects
Signal Transduction
Mitochondria pathology
Mitochondrial Proteins metabolism
Neoplasms pathology
Plasma Gases pharmacology
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26942565
- Full Text :
- https://doi.org/10.18632/oncotarget.7889