Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination

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.