title: Tumor-selective mitochondrial network collapse induced by atmospheric gas plasma-activated medium.
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.
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Tokyo, Japan.|Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Physics, College of Science and Technology, Nihon University, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asai
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Tokyo, Japan.|Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Physics, College of Science and Technology, Nihon University, Tokyo, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Sahara
authors.affiliation: The National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Koguchi
authors.affiliation: Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.affiliation: Department of Dermatology, Nihon University Surugadai Hospital, Saitama, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Suzuki-Karasaki
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Tokyo, Japan.|Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Tokyo, Japan.|Division of Physiology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki-Karasaki
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D058626:Plasma Gases / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D024101:Mitochondrial Proteins; D016877:Oxidants; D058626:Plasma Gases; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide
keywords: AGP-activated medium; mitochondrial network; non-thermal atmospheric gas plasma (AGP); reactive oxygen species (ROS); tumor-selective killing