Oncotarget

Research Papers:

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

Kosuke Saito, Tomohiko Asai, Kyoko Fujiwara, Junki Sahara, Haruhisa Koguchi, Noboru Fukuda, Miki Suzuki-Karasaki, Masayoshi Soma and Yoshihiro Suzuki-Karasaki _

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Oncotarget. 2016; 7:19910-19927. https://doi.org/10.18632/oncotarget.7889

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Abstract

Kosuke Saito1,2, Tomohiko Asai3, Kyoko Fujiwara1,2, Junki Sahara3, Haruhisa Koguchi4, Noboru Fukuda5, Miki Suzuki-Karasaki6, Masayoshi Soma1,2, Yoshihiro Suzuki-Karasaki1,7

1Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Tokyo, Japan

2Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

3Department of Physics, College of Science and Technology, Nihon University, Tokyo, Japan

4The National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan

5Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

6Department of Dermatology, Nihon University Surugadai Hospital, Saitama, Japan

7Division of Physiology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan

Correspondence to:

Yoshihiro Suzuki-Karasaki, e-mail: [email protected]

Keywords: non-thermal atmospheric gas plasma (AGP), AGP-activated medium, mitochondrial network, reactive oxygen species (ROS), tumor-selective killing

Received: November 19, 2015     Accepted: February 09, 2016     Published: March 03, 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.


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