Cold atmospheric-pressure nitrogen plasma induces the production of reactive nitrogen species and cell death by increasing intracellular calcium in HEK293T cells

Iuchi, Katsuya; Morisada, Yukina; Yoshino, Yuri; Himuro, Takahiro; Saito, Yoji; Murakami, Tomoyuki; Higuchi, Hisashi

doi:10.1016/j.abb.2018.07.015

Cited by 26 publications

(24 citation statements)

References 46 publications

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“…To obtain an equilibrated cocktail of RONS and avoiding a loss of anti-cancer selectivity [36], for further work we selected APPJ-treated PAR. In order to adjust the production of RONS, plasma parameters like gas flow [36,55], distance of the nozzle [7,36,55], working gas composition [56][57][58][59] and here, device configuration [60,61] are of paramount importance to adjust the composition of RONS generated in the liquid, and the conditions selected here followed previous works of our group [36,62].…”

Section: Discussionmentioning

confidence: 99%

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Mateu-Sanz

Tornín

Brulin

et al. 2020

Cancers

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Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer’s saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Mateu-Sanz

Tornín

Brulin

et al. 2020

Cancers

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“…This suggests that the use of NTP as an alternative therapy can overcome the In particular, NTPAM is useful because it has an anticancer effect similar to that of existing NTP and can be directly applied to tumors [29][30][31]. The anticancer effects of NTP are broadly related to mechanisms such as apoptosis induction through ROS generation and cytoskeletal modulation [6,31,32], but the detailed underlying mechanisms are unclear. To our knowledge, there have been few studies concerning the mechanism by which NTPAM mediates its anticancer effects.…”

Section: Discussionmentioning

confidence: 99%

Head and Neck Cancer Cell Death due to Mitochondrial Damage Induced by Reactive Oxygen Species from Nonthermal Plasma‐Activated Media: Based on Transcriptomic Analysis

Won

Kang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mitochondrial targeted therapy is a next-generation therapeutic approach for cancer that is refractory to conventional treatments. Mitochondrial damage caused by the excessive accumulation of reactive oxygen species (ROS) is a principle of mitochondrial targeted therapy. ROS in nonthermal plasma-activated media (NTPAM) are known to mediate anticancer effects in various cancers including head and neck cancer (HNC). However, the signaling mechanism of HNC cell death via NTPAM-induced ROS has not been fully elucidated. This study evaluated the anticancer effects of NTPAM in HNC and investigated the mechanism using transcriptomic analysis. The viability of HNC cells decreased after NTPAM treatment due to enhanced apoptosis. A human fibroblast cell line and three HNC cell lines were profiled by RNA sequencing. In total, 1 610 differentially expressed genes were identified. Pathway analysis showed that activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were upstream regulators. Mitochondrial damage was induced by NTPAM, which was associated with enhancements of mitochondrial ROS (mtROS) and ATF4/CHOP regulation. These results suggest that NTPAM induces HNC cell death through the upregulation of ATF4/CHOP activity by damaging mitochondria via excessive mtROS accumulation, similar to mitochondrial targeted therapy.

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“…They were also not far from some of the rotational temperatures observed in microwave plasmas [ 165 ] and may in fact be energetic enough to excite some analyte metals and produce ions [ 157 ]. While this device was operated with He as the plasma source gas, most cold plasma devices can operate with either Ar [ 166 ] or air [ 167 ] or nitrogen [ 168 ].…”

Section: Putting the Pieces Together On A Plasma Instrument Feasibilitymentioning

confidence: 99%

Moving toward a Handheld “Plasma” Spectrometer for Elemental Analysis, Putting the Power of the Atom (Ion) in the Palm of Your Hand

Buckley

Doherty

2021

Molecules

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Many of the current innovations in instrument design have been focused on making them smaller, more rugged, and eventually field transportable. The ultimate application is obvious, carrying the instrument to the field for real time sample analysis without the need for a support laboratory. Real time data are priceless when screening either biological or environmental samples, as mitigation strategies can be initiated immediately upon the discovery that contaminant metals are present in a location they were not intended to be. Additionally, smaller “handheld” instruments generally require less sample for analysis, possibly increasing sensitivity, another advantage to instrument miniaturization. While many other instruments can be made smaller just by using available micro-technologies (e.g., eNose), shrinking an ICP-MS or AES to something someone might carry in a backpack or pocket is now closer to reality than in the past, and can be traced to its origins based on a component-by-component evaluation. While the optical and mass spectrometers continue to shrink in size, the ion/excitation source remains a challenge as a tradeoff exists between excitation capabilities and the power requirements for the plasma’s generation. Other supporting elements have only recently become small enough for transport. A systematic review of both where the plasma spectrometer started and the evolution of technologies currently available may provide the roadmap necessary to miniaturize the spectrometer. We identify criteria on a component-by-component basis that need to be addressed in designing a miniaturized device and recognize components (e.g., source) that probably require further optimization. For example, the excitation/ionization source must be energetic enough to take a metal from a solid state to its ionic state. Previously, a plasma required a radio frequency generator or high-power DC source, but excitation can now be accomplished with non-thermal (cold) plasma sources. Sample introduction, for solids, liquids, and gasses, presents challenges for all sources in a field instrument. Next, the interface between source and a mass detector usually requires pressure reduction techniques to get an ion from plasma to the spectrometer. Currently, plasma mass spectrometers are field ready but not necessarily handheld. Optical emission spectrometers are already capable of getting photons to the detector but could eventually be connected to your phone. Inert plasma gas generation is close to field ready if nitrogen generators can be miniaturized. Many of these components are already commercially available or at least have been reported in the literature. Comparisons to other “handheld” elemental analysis devices that employ XRF, LIBS, and electrochemical methods (and their limitations) demonstrate that a “cold” plasma-based spectrometer can be more than competitive. Migrating the cold plasma from an emission only source to a mass spectrometer source, would allow both analyte identification and potentially source apportionment through isotopic fingerprinting, and may be the last major hurdle to overcome. Finally, we offer a possible design to aid in making the cold plasma source more applicable to a field deployment.

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Cold atmospheric-pressure nitrogen plasma induces the production of reactive nitrogen species and cell death by increasing intracellular calcium in HEK293T cells

Cited by 26 publications

References 46 publications

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Cold Plasma-Treated Ringer’s Saline: A Weapon to Target Osteosarcoma

Head and Neck Cancer Cell Death due to Mitochondrial Damage Induced by Reactive Oxygen Species from Nonthermal Plasma‐Activated Media: Based on Transcriptomic Analysis

Moving toward a Handheld “Plasma” Spectrometer for Elemental Analysis, Putting the Power of the Atom (Ion) in the Palm of Your Hand

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