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  • Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination.

Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination.

Cells (2020-03-07)
Sun-Yong Kim, Hyo Jeong Kim, Haeng Jun Kim, Chul-Ho Kim
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
N-Acetyl-L-cysteine, BioReagent, suitable for cell culture
Sigma-Aldrich
Bafilomycin A1 from Streptomyces griseus, ≥90% (HPLC)
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RIPA Buffer
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Everolimus, ≥95% (HPLC)
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ECO TWEEN® 20, viscous liquid
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Rapamycin, Ready Made Solution, 2.5 mg/mL in DMSO (2.74 mM), from Streptomyces hygroscopicus
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TWEEN® 20, viscous liquid
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Amyloid Protein Non-Aβ Component, ≥80% (HPLC)
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Cycloheximide, from microbial, ≥94% (TLC)
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Imatinib
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Monoclonal Anti-mTOR antibody produced in mouse, clone GT6611, affinity isolated antibody