scholarly journals Cold atmospheric plasma induces GSDME-dependent pyroptotic signaling pathway via ROS generation in tumor cells

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Xiaorui Yang ◽  
Guodong Chen ◽  
Kwan Ngok Yu ◽  
Miaomiao Yang ◽  
Shengjie Peng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Tumor Cells ◽  
Atmospheric Plasma ◽  
Ros Generation ◽  
Cold Atmospheric Plasma

Targeting Protective Catalase of Tumor Cells with Cold Atmospheric Plasma- Activated Medium (PAM)

2018 ◽  
Vol 18 (6) ◽  
pp. 784-804 ◽  
Author(s):  
Georg Bauer
Keyword(s):  
Control System ◽  
Singlet Oxygen ◽  
Tumor Cells ◽  
Plasma Potential ◽  
Atmospheric Plasma ◽  
Antitumor Action ◽  
Active Principle ◽  
Reaction Products ◽  
Cold Atmospheric Plasma

Background: Application of cold atmospheric plasma to medium generates “plasma-activated medium” that induces apoptosis selectively in tumor cells and that has an antitumor effect in vivo. The underlying mechanisms are not well understood. Objective: Elucidation of potential chemical interactions within plasma-activated medium and of reactions of medium components with specific target structures of tumor cells should allow to define the active principle in plasma activated medium. Methods: Established knowledge of intercellular apoptosis-inducing reactive oxygen/nitrogen species-dependent signaling and its control by membrane-associated catalase and SOD was reviewed. Model experiments using extracellular singlet oxygen were analyzed with respect to catalase inactivation and their relevance for the antitumor action of cold atmospheric plasma. Potential interactions of this tumor cell-specific control system with components of plasma-activated medium or its reaction products were discussed within the scope of the reviewed signaling principles. Results: None of the long-lived species found in plasma-activated medium, such as nitrite and H2O2, nor OCl- or .NO seemed to have the potential to interfere with catalase-dependent control of apoptosis-inducing signaling of tumor cells when acting alone. However, the combination of H2O2 and nitrite might generate peroxynitrite. The protonation of peroxnitrite to peroxynitrous acid allows for the generation of hydroxyl radicals that react with H2O2, leading to the formation of hydroperoxide radicals. These allow for singlet oxygen generation and inactivation of membrane-associated catalase through an autoamplificatory mechanism, followed by intercellular apoptosis-inducing signaling. Conclusion: Nitrite and H2O2 in plasma-activated medium establish singlet oxygen-dependent interference selectively with the control system of tumor cells.

scholarly journals Selective treatments of prostate tumor cells with a cold atmospheric plasma jet

2020 ◽  
Vol 17-18 ◽  
pp. 100098 ◽  
Author(s):  
Mohamed Fofana ◽  
Julio Buñay ◽  
Florian Judée ◽  
Silvère Baron ◽  
Sébastien Menecier ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Plasma Jet ◽  
Prostate Tumor ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma ◽  
Prostate Tumor Cells

scholarly journals Low dose Cold Atmospheric Plasma induces membrane oxidation, stimulates endocytosis and enhances uptake of nanomaterials in Glioblastoma multiforme cells

2019 ◽  
Author(s):  
Zhonglei He ◽  
Kangze Liu ◽  
Laurence Scally ◽  
Eline Manaloto ◽  
Sebnem Gunes ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Membrane Damage ◽  
Cellular Membrane ◽  
Atmospheric Plasma ◽  
Ros Generation ◽  
Main Role ◽  
Cancer Therapies ◽  
Membrane Repair ◽  
Cold Atmospheric Plasma ◽  
Therapy And Diagnosis

AbstractCold atmospheric plasma (CAP) has demonstrated synergistic cytotoxic effects with nanoparticles, especially promoting the uptake and accumulation of nanoparticles inside cells. However, the mechanisms driving the effects need to be explored. In this study, we investigate the enhanced uptake of theranostic nanomaterials by CAP. Numerical modelling of the uptake of gold nanoparticle into U373MG Glioblastoma multiforme (GBM) cells predicts that CAP may introduce a new uptake route. We demonstrate that cell membrane repair pathways play the main role in this stimulated new uptake route, following non-toxic doses of dielectric barrier discharge CAP (30 s, 75 kV). CAP treatment induces cellular membrane damage, mainly via lipid peroxidation as a result of reactive oxygen species (ROS) generation. Membranes rich in peroxidated lipids are then trafficked into cells via membrane repairing endocytosis. We confirm that the enhanced uptake of nanomaterials is clathrin-dependent using chemical inhibitors and silencing of gene expression. Therefore, CAP-stimulated membrane repair increases endocytosis and accelerates the uptake of gold nanoparticles into U373MG cells after CAP treatment. Our data demonstrate the utility of CAP to model membrane oxidative damage in cells and characterise a previously unreported mechanism of membrane repair to trigger nanomaterial uptake which will be useful for developing more efficient deliveries of nanoparticles and pharmaceuticals into cancer cells for tumour therapy and diagnosis. This mechanism of RONS-induced endocytosis will also be of relevance to other cancer therapies that induce an increase in extracellular RONS.

scholarly journals COLD ATMOSPHERIC PLASMA DIFFERENTIALLY AFFECTS CELL RENEWAL AND DIFFERENTIATION OF STEM CELLS AND APC-DEFICIENT-DERIVED TUMOR CELLS IN INTESTINAL ORGANOIDS

2021 ◽  
Author(s):  
Alia Hadefi ◽  
Morgane Leprovots ◽  
Max Thulliez ◽  
Orianne Bastin ◽  
Anne Lefort ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Cells ◽  
Ex Vivo ◽  
Biological Effects ◽  
Three Dimensional ◽  
Atmospheric Plasma ◽  
Cell Renewal ◽  
Epithelial Stem Cells ◽  
Cold Atmospheric Plasma ◽  
Ex Vivo Culture

Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with global response to oxidative stress, fetal-like regeneration reprogramming and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.

scholarly journals Dynamics of Singlet Oxygen-Triggered, RONS-Based Apoptosis Induction after Treatment of Tumor Cells with Cold Atmospheric Plasma or Plasma-Activated Medium

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Georg Bauer ◽  
Dominika Sersenová ◽  
David B. Graves ◽  
Zdenko Machala
Keyword(s):  
Singlet Oxygen ◽  
Tumor Cells ◽  
Dynamic Process ◽  
Bystander Effect ◽  
Atmospheric Plasma ◽  
Specific Response ◽  
Apoptosis Induction ◽  
Cold Atmospheric Plasma ◽  
Low Efficiency ◽  
Triggering Process

Abstract Treatment of tumor cells with cold atmospheric plasma (CAP) or with plasma-activated medium (PAM) leads to a biochemical imprint on these cells. This imprint is mediated by primary singlet oxygen, which is mainly generated through the interaction between CAP-derived H2O2 and NO2−. This imprint is induced with a low efficiency as local inactivation of a few membrane-associated catalase molecules. As sustained generation of secondary singlet oxygen by the tumor cells is activated at the site of the imprint, a rapid bystander effect-like spreading of secondary singlet oxygen generation and catalase inactivation within the cell population is thus induced. This highly dynamic process is essentially driven by NOX1 and NOS of the tumor cells, and finally leads to intercellular RONS-driven apoptosis induction. This dynamic process can be studied by kinetic analysis, combined with the use of specific inhibitors at defined time intervals. Alternatively, it can be demonstrated and quantified by transfer experiments, where pretreated cells are mixed with untreated cells and bystander signaling is determined. These studies allow to conclude that the specific response of tumor cells to generate secondary singlet oxygen is the essential motor for their self-destruction, after a singlet oxygen-mediated triggering process by CAP or PAM.

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