Plasma‐activated medium as an innovative anticancer strategy: Insight into its cellular and molecular impact on in vitro leukemia cells

Abstract

Cold atmospheric plasma (CAP) has received attention as a potential anticancer strategy. In this study, culture medium was exposed to a microsecondpulsed dielectric barrier discharge jet to produce plasma-activated medium (PAM). On the T-lymphoblastic cell line, PAM induced apoptosis through the activation of the intrinsic pathway and inhibited the cell-cycle progression. The use of the scavengers N-acetylcysteine or O-phenantroline significantly decreased the PAM proapoptotic activity. The genetic impact of PAM on TK6 cells was assessed, resulting in an increased micronuclei frequency. PAM exhibited cytotoxic effects even on leukemia cells cultivated in hypoxia, which plays a critical role in promoting chemoresistance. PAM was also tested on normal lymphocytes, showing its partial selectivity. Taken together, these results contribute to understand the pharmacotoxicological profile of CAP.

Differential Effect of Non-Thermal Plasma RONS on Two Human Leukemic Cell Populations

“…To address this hypothesis, we measured the NTP-dependent cytotoxicity in both cell lines. Previous studies demonstrated that application of NTP to Jurkat cells resulted in increased oxidative stress and stimulation of pro-apoptotic pathways [ 26 , 27 , 28 ]. In agreement with these studies, we observed that exposure of Jurkat cells to nsDBD plasma induced a frequency-dependent decrease in cell viability, with considerable cytotoxicity observed at 105 Hz ( Figure 3 a).…”

“…Investigations involving Jurkat cells demonstrated NTP-mediated cytotoxicity and increased cellular stress in these lymphoblastic leukemia cells [ 28 , 47 ]. NTP exposure was shown to stimulate the intrinsic apoptotic pathway in these cells through activation of caspase-8 and upregulation of pro-apoptotic proteins [ 26 , 27 , 28 , 47 ]. Genotoxic effects of NTP were also demonstrated through inhibition of cell cycle progression and increased micronuclei in NTP-exposed Jurkat cells, which were reversed when plasma RONS were scavenged by NAC [ 26 ].…”

“…NTP exposure was shown to stimulate the intrinsic apoptotic pathway in these cells through activation of caspase-8 and upregulation of pro-apoptotic proteins [ 26 , 27 , 28 , 47 ]. Genotoxic effects of NTP were also demonstrated through inhibition of cell cycle progression and increased micronuclei in NTP-exposed Jurkat cells, which were reversed when plasma RONS were scavenged by NAC [ 26 ]. On the other hand, THP-1 cells have been shown to be quite resistant to the direct cytotoxic effects of NTP [ 48 ].…”

Plasma Treatment Limits Cutaneous Squamous Cell Carcinoma Development In Vitro and In Vivo

“…For this, 8-hydroxy-2′—deoxyguanosine (8-OHdG) was quantified, being one of the predominant forms of ROS-induced oxidative DNA alteration [ 55 ]. Although several reports have speculated DNA-damaging properties of plasma treatment [ 56 , 57 , 58 , 59 , 60 ], these reports usually did not use gold-standard assays of genotoxic research or only partially adhered to them to confirm their results. Our previous reports did not find, for instance, an increase in micronucleus formation following plasma treatment [ 20 , 35 , 61 ], being a gold standard assay, according to the OECD (Organisation for Economic Co-operation and Development) for toxicity research.…”

Special issue: Advanced applications of plasmas in Life Sciences 2020

“…The issue of the penetration of RONS in the skin tissue is addressed in their paper by Duan et al [ 6 ] ; this is a relevant topic for the optimization of plasma processes in clinic. Satisfactory effects of plasma‐generated RONS on proteins are discussed in the two papers by Krewing et al [ 7 ] and by Sasaki et al [ 8 ] The effect of CAP treatments on leukemia cells and on mitochondria, instead, are reviewed in the papers by Turrini et al [ 9 ] and Yan et al [ 10 ] respectively. Nakamura et al [ 11 ] described how tuning the relative flow rate of O 2 and N 2 in the feed of a novel plasma source can generate plasma‐activated media with different relative amounts of RONS, thus with different potential antitumor activities.…”