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Open AccessArticle

Combination Treatment with Cold Physical Plasma and Pulsed Electric Fields Augments ROS Production and Cytotoxicity in Lymphoma

ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), a Member of the Leibniz Research Alliance Leibniz Health Technology, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany
Institute of Physics, University of Rostock, Albert-Einstein-Str. 23-24, 18059 Rostock, Germany
Institute for Hygiene and Environmental Medicine, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany
Authors to whom correspondence should be addressed.
Cancers 2020, 12(4), 845;
Received: 13 March 2020 / Revised: 28 March 2020 / Accepted: 29 March 2020 / Published: 31 March 2020
New approaches in oncotherapy rely on the combination of different treatments to enhance the efficacy of established monotherapies. Pulsed electric fields (PEFs) are an established method (electrochemotherapy) for enhancing cellular drug uptake while cold physical plasma is an emerging and promising anticancer technology. This study aimed to combine both technologies to elucidate their cytotoxic potential as well as the underlying mechanisms of the effects observed. An electric field generator (0.9–1.0 kV/cm and 100-μs pulse duration) and an atmospheric pressure argon plasma jet were employed for the treatment of lymphoma cell lines as a model system. PEF but not plasma treatment induced cell membrane permeabilization. Additive cytotoxicity was observed for the metabolic activity and viability of the cells while the sequence of treatment in the combination played only a minor role. Intriguingly, a parallel combination was more effective compared to a 15-min pause between both treatment regimens. A combination effect was also found for lipid peroxidation; however, none could be observed in the cytosolic and mitochondrial reactive oxygen species (ROS) production. The supplementation with either antioxidant, a pan-caspase-inhibitor or a ferroptosis inhibitor, all partially rescued lymphoma cells from terminal cell death, which contributes to the mechanistic understanding of this combination treatment. View Full-Text
Keywords: PEF; plasma medicine; reactive oxygen and nitrogen species PEF; plasma medicine; reactive oxygen and nitrogen species
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Wolff, C.M.; Kolb, J.F.; Weltmann, K.-D.; von Woedtke, T.; Bekeschus, S. Combination Treatment with Cold Physical Plasma and Pulsed Electric Fields Augments ROS Production and Cytotoxicity in Lymphoma. Cancers 2020, 12, 845.

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