Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination

Cells. 2020 Mar 2;9(3):595. doi: 10.3390/cells9030595.

Abstract

Non-thermal plasma (NTP) has been studied as a novel therapeutic tool for cancer that does not damage healthy cells. In this study, we show that NTP-treated solutions (NTS) can induce death in various leukemia cells through mechanistic target of rapamycin (mTOR) ubiquitination. Previously, we manufactured and demonstrated the efficacy of NTS in solid cancers. NTS did not exhibit any deleterious side effects, such as acute death or weight loss in nude mice. In the present study, NTS induced cell death in myeloid leukemia cells, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We found that mTOR was downregulated in NTS-treated cells via the ubiquitin-proteasome system (UPS). We also identified 'really interesting new gene' finger protein 126 (RNF126) as a novel binding protein for mTOR through protein arrays and determined the role of E3 ligase in NTS-induced mTOR ubiquitination. NTS-derived reactive oxygen species (ROS) affected RNF126 expression and lysosomal dysfunction. These findings suggest that NTS has potential antileukemic effects through RNF126-mediated mTOR ubiquitination with no deleterious side effects. Thus, NTS may represent a new therapeutic method for chemotherapy-resistant leukemia.

Keywords: Non-thermal plasma; RNF126; leukemia; lysosome; mTOR; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Humans
  • K562 Cells
  • Leukemia / metabolism*
  • Leukemia / therapy*
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Plasma Gases / pharmacology*
  • TOR Serine-Threonine Kinases / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Plasma Gases
  • RNF126 protein, human
  • Ubiquitin-Protein Ligases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse