Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination

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Sun-Yong Kim1,2, Hyo Jeong Kim1,2,3, Haeng Jun Kim1,2,3

  • 1Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Korea.

Cells
|March 6, 2020
PubMed

Insights

Non-thermal plasma solutions induce leukemia cell death by targeting mTOR ubiquitination. This novel approach shows potential as a safe therapy for leukemia, including chemotherapy-resistant types.

Area of Science:

  • Biomedical Engineering
  • Cancer Research
  • Plasma Medicine

Background:

  • Non-thermal plasma (NTP) is an emerging therapeutic modality for cancer treatment.
  • Previous studies demonstrated NTP-treated solutions (NTS) efficacy in solid tumors with no observed adverse effects in mice.

Purpose of the Study:

  • To investigate the efficacy of NTS in treating myeloid leukemia.
  • To elucidate the molecular mechanisms underlying NTS-induced leukemia cell death, focusing on mechanistic target of rapamycin (mTOR) ubiquitination.

Main Methods:

  • Treatment of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells with NTS.
  • Analysis of mTOR downregulation via the ubiquitin-proteasome system (UPS).
  • Identification of RNF126 as an mTOR binding protein using protein arrays and assessment of its role in ubiquitination.

Main Results:

  • NTS effectively induced cell death in AML and CML cell lines.
  • mTOR was downregulated in NTS-treated cells through the UPS.
  • RNF126 was identified as a novel mTOR binding protein, crucial for NTS-induced mTOR ubiquitination.
  • NTS-derived reactive oxygen species (ROS) influenced RNF126 expression and lysosomal function.

Conclusions:

  • NTS exhibits potential antileukemic effects against myeloid leukemia via RNF126-mediated mTOR ubiquitination.
  • The mechanism involves ROS-induced effects on RNF126 and lysosomal pathways.
  • NTS represents a promising, safe therapeutic strategy for leukemia, potentially overcoming chemotherapy resistance.
Keywords:
Non-thermal plasmaRNF126leukemialysosomemTORubiquitination

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