Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Synergistic anticancer effect of plasma-activated infusion and salinomycin by targeting autophagy and mitochondrial morphology

Takashi Ando, Manami Suzuki-Karasaki, Miki Suzuki-Karasaki, Jiro Ichikawa, Toyoko Ochiai, Yukihiro Yoshida, Hirotaka Haro, Yoshihiro Suzuki-Karasaki
doi: https://doi.org/10.1101/2020.10.14.340208
Takashi Ando
1Department of Orthopedic Surgery, Yamanashi University School of Medicine, Yamanashi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: tando@mtg.biglobe.ne.jp andou@yamanashi.ac.jp yoshisk181@pcbl.or.jp suzuki.pcbl@gmail.com
Manami Suzuki-Karasaki
2Plasma ChemiBio Laboratory, Nasushiobara, Tochigi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miki Suzuki-Karasaki
2Plasma ChemiBio Laboratory, Nasushiobara, Tochigi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jiro Ichikawa
1Department of Orthopedic Surgery, Yamanashi University School of Medicine, Yamanashi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toyoko Ochiai
2Plasma ChemiBio Laboratory, Nasushiobara, Tochigi, Japan
3Department of Dermatology, Nihon University Hospital, Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yukihiro Yoshida
4Department of Orthopedic Surgery, Nihon University School of Medicine, Tokyo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hirotaka Haro
1Department of Orthopedic Surgery, Yamanashi University School of Medicine, Yamanashi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshihiro Suzuki-Karasaki
2Plasma ChemiBio Laboratory, Nasushiobara, Tochigi, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: tando@mtg.biglobe.ne.jp andou@yamanashi.ac.jp yoshisk181@pcbl.or.jp suzuki.pcbl@gmail.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Non-thermal atmospheric plasma (NTAP)-activated liquids have emerged as new promising anticancer agents because they preferentially injure malignant cells. Here, we report plasma-activated infusion (PAI) as a novel NTAP-based anti-neoplastic agent. PAI was prepared by irradiating helium NTAP to form a clinically approved infusion fluid. PAI dose-dependently killed malignant melanoma and osteosarcoma cell lines showed much lower cytotoxic effects on dermal and lung fibroblasts. We found that PAI and salinomycin (Sal), an emerging anti-cancer stem cell agent, mutually operated as adjuvants. Combined administration of PAI and Sal was much more effective than single agent application in reducing the growth and lung metastasis of osteosarcoma allografts with minimal adverse effects. Mechanistically, PAI explicitly induced necroptosis and increased the phosphorylation of receptor-interacting protein 1/3 in a rapid and transient manner. PAI also suppressed the ambient autophagic flux by activating the mammalian target of rapamycin pathway. PAI increased the phosphorylation of Raptor, Rictor, and p70-S6 kinase, along with decreased LC3-I/II expression. In contrast, Sal promoted autophagy. Moreover, Sal exacerbated the mitochondrial network collapse caused by PAI, resulting in aberrant clustering of fragmented mitochondrial in a tumor-specific manner. Our findings suggest that combined administration of PAI and Sal is a promising approach for treating these apoptosis-resistant cancers.

Competing Interest Statement

Ma.S.K. (Manami Suzuki-Karasaki), Mi.S.K. (Miki Suzuki-Karasaki), and Y.S.K. are employees of the Non-Profit Institute Plasma ChemiBio Laboratory. The remaining authors have no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted October 15, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Synergistic anticancer effect of plasma-activated infusion and salinomycin by targeting autophagy and mitochondrial morphology
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Synergistic anticancer effect of plasma-activated infusion and salinomycin by targeting autophagy and mitochondrial morphology
Takashi Ando, Manami Suzuki-Karasaki, Miki Suzuki-Karasaki, Jiro Ichikawa, Toyoko Ochiai, Yukihiro Yoshida, Hirotaka Haro, Yoshihiro Suzuki-Karasaki
bioRxiv 2020.10.14.340208; doi: https://doi.org/10.1101/2020.10.14.340208
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Synergistic anticancer effect of plasma-activated infusion and salinomycin by targeting autophagy and mitochondrial morphology
Takashi Ando, Manami Suzuki-Karasaki, Miki Suzuki-Karasaki, Jiro Ichikawa, Toyoko Ochiai, Yukihiro Yoshida, Hirotaka Haro, Yoshihiro Suzuki-Karasaki
bioRxiv 2020.10.14.340208; doi: https://doi.org/10.1101/2020.10.14.340208

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4838)
  • Biochemistry (10739)
  • Bioengineering (8018)
  • Bioinformatics (27196)
  • Biophysics (13941)
  • Cancer Biology (11087)
  • Cell Biology (15999)
  • Clinical Trials (138)
  • Developmental Biology (8759)
  • Ecology (13247)
  • Epidemiology (2067)
  • Evolutionary Biology (17322)
  • Genetics (11667)
  • Genomics (15887)
  • Immunology (10996)
  • Microbiology (26002)
  • Molecular Biology (10608)
  • Neuroscience (56369)
  • Paleontology (417)
  • Pathology (1729)
  • Pharmacology and Toxicology (2999)
  • Physiology (4530)
  • Plant Biology (9593)
  • Scientific Communication and Education (1610)
  • Synthetic Biology (2672)
  • Systems Biology (6960)
  • Zoology (1508)