Tumor-selective mitochondrial network collapse induced by atmospheric gas plasma-activated medium.

Content Provider	Europe PMC
Author	Saito, Kosuke Asai, Tomohiko Fujiwara, Kyoko Sahara, Junki Koguchi, Haruhisa Fukuda, Noboru Suzuki-Karasaki, Miki Soma, Masayoshi Suzuki-Karasaki, Yoshihiro
Copyright 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.
Journal	Oncotarget
Volume Number	7
PubMed Central reference number	PMC4991427
Issue Number	15
PubMed reference number	26942565
e-ISSN	19492553
DOI	10.18632/oncotarget.7889
Language	English
Publisher	Impact Journals LLC
Publisher Date	2016-04-01
Access Restriction	Open
Rights License	This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: © 2016 Saito et al.
Subject Keyword	non-thermal atmospheric gas plasma (AGP) AGP-activated medium mitochondrial network reactive oxygen species (ROS) tumor-selective killing
Content Type	Text
Resource Type	Article
Subject	Oncology