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Volume 23
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10.3390/ijms23031124
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Article

Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering

by
Manami Suzuki-Karasaki
1,2,
Takashi Ando
3,
Yushi Ochiai
1,
Kenta Kawahara
2,
Miki Suzuki-Karasaki
1,
Hideki Nakayama
2 and
Yoshihiro Suzuki-Karasaki
1,*
1
Department of Research and Development, Plasma ChemiBio Laboratory, Nasushiobara 329-2813, Japan
2
Department of Oral and Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
3
Department of Orthopaedic Surgery, Yamanashi University School of Medicine, Yamanashi 409-3898, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(3), 1124; https://doi.org/10.3390/ijms23031124
Submission received: 24 November 2021 / Revised: 14 January 2022 / Accepted: 17 January 2022 / Published: 20 January 2022
(This article belongs to the Collection Feature Papers in Molecular Oncology)
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Abstract

Intractable cancers such as osteosarcoma (OS) and oral cancer (OC) are highly refractory, recurrent, and metastatic once developed, and their prognosis is still disappointing. Tumor-targeted therapy, which eliminates cancers effectively and safely, is the current clinical choice. Since aggressive tumors are substantially resistant to multidisciplinary therapies that target apoptosis, tumor-specific activation of another cell death modality is a promising avenue for meeting this goal. Here, we report that a cold atmospheric air plasma-activated medium (APAM) can kill OS and OC by causing a unique mitochondrial clustering. This event was named monopolar perinuclear mitochondrial clustering (MPMC) based on its characteristic unipolar mitochondrial perinuclear accumulation. The APAM caused apoptotic and nonapoptotic cell death. The APAM increased mitochondrial ROS (mROS) and cell death, and the antioxidants such as N-acetylcysteine (NAC) prevented them. MPMC occurred following mitochondrial fragmentation, which coincided with nuclear damages. MPMC was accompanied by mitochondrial lipid peroxide (mLPO) accumulation and prevented by NAC, Ferrostatin-1, and Nocodazole. In contrast, the APAM induced minimal cell death, mROS generation, mLPO accumulation, and MPMC in fibroblasts. These results suggest that MPMC occurs in a tumor-specific manner via mitochondrial oxidative stress and microtubule-driven mitochondrial motility. MPMC induction might serve as a promising target for exerting tumor-specific cytotoxicity.
Keywords: cancer; ROS; perinuclear mitochondrial clustering; mitochondrial network; mitochondrial positioning; plasma-activated medium; cell death; lipid peroxidation cancer; ROS; perinuclear mitochondrial clustering; mitochondrial network; mitochondrial positioning; plasma-activated medium; cell death; lipid peroxidation

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MDPI and ACS Style

Suzuki-Karasaki, M.; Ando, T.; Ochiai, Y.; Kawahara, K.; Suzuki-Karasaki, M.; Nakayama, H.; Suzuki-Karasaki, Y. Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering. Int. J. Mol. Sci. 2022, 23, 1124. https://doi.org/10.3390/ijms23031124

AMA Style

Suzuki-Karasaki M, Ando T, Ochiai Y, Kawahara K, Suzuki-Karasaki M, Nakayama H, Suzuki-Karasaki Y. Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering. International Journal of Molecular Sciences. 2022; 23(3):1124. https://doi.org/10.3390/ijms23031124

Chicago/Turabian Style

Suzuki-Karasaki, Manami, Takashi Ando, Yushi Ochiai, Kenta Kawahara, Miki Suzuki-Karasaki, Hideki Nakayama, and Yoshihiro Suzuki-Karasaki. 2022. "Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering" International Journal of Molecular Sciences 23, no. 3: 1124. https://doi.org/10.3390/ijms23031124

APA Style

Suzuki-Karasaki, M., Ando, T., Ochiai, Y., Kawahara, K., Suzuki-Karasaki, M., Nakayama, H., & Suzuki-Karasaki, Y. (2022). Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering. International Journal of Molecular Sciences, 23(3), 1124. https://doi.org/10.3390/ijms23031124

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