Tumor-selective mitochondrial network collapse induced by atmospheric gas plasma-activated medium

Abstract

Non-thermal atmospheric gas plasma (AGP) exhibits cytotoxicity against malignant cells with minimal cytotoxicity toward normal cells. However, the mechanisms of its tumor-selective cytotoxicity remain unclear. Here we report that AGP-activated medium increases caspase-independent cell death and mitochondrial network collapse in a panel of human cancer cells, but not in non-transformed cells. AGP irradiation stimulated reactive oxygen species (ROS) generation in AGP-activated medium, and in turn the resulting stable ROS, most likely hydrogen peroxide (H2O2), activated intracellular ROS generation and mitochondrial ROS (mROS) accumulation. Culture in AGP-activated medium resulted in cell death and excessive mitochondrial fragmentation and clustering, and these responses were inhibited by ROS scavengers. AGP-activated medium also increased dynamin-related protein 1-dependent mitochondrial fission in a tumor-specific manner, and H2O2 administration showed similar effects. Moreover, the vulnerability of tumor cells to mitochondrial network collapse appeared to result from their higher sensitivity to mROS accumulation induced by AGP-activated medium or H2O2. The present findings expand our previous observations on death receptor-mediated tumor-selective cell killing and reinforce the importance of mitochondrial network remodeling as a powerful target for tumor-selective cancer treatment.

A Comparison of Floating-Electrode DBD and kINPen Jet: Plasma Parameters to Achieve Similar Growth Reduction in Colon Cancer Cells Under Standardized Conditions

“…A combination of different plasma properties is also possible as seen with bacteria [81][82][83]. Corroborating results of the jet plasma in the present work, presence and concentration of H 2 O 2 strongly correlated with cytotoxic effects of the kINPen [84][85][86] and other jet and DBD plasma sources [87][88][89][90], especially plasma-treated liquids [91][92][93]. Yet, in a helium/oxygen plasma jet, we previously demonstrated cytotoxicity correlating with short-lived species supporting the generation of hypochlorous acid in aqueous media [94].…”

Loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis and leads to apoptotic cell death in Schizosaccharomyces pombe

“…Mitochondrial fragmentation correlates with apoptosis in mammals [25][26][27]. We went on to examine the mitochondrial morphology in the wild-type cells and cells depleted of ppr3, ppr4, ppr6, or ppr10 by fluorescence microscopy after MitoTracker staining.…”

Impact of exudative diathesis induced by selenium deficiency on LncRNAs and their roles in the oxidative reduction process in broiler chick veins

“…H 2 O 2 can induce oxidative stress in cells [50]. However, Se play adverse role in the oxidative reduction process.…”