scholarly journals Acidified Nitrite Contributes to the Antitumor Effect of Cold Atmospheric Plasma on Melanoma Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3757
Author(s):  
Tom Zimmermann ◽  
Lisa A Gebhardt ◽  
Lucas Kreiss ◽  
Christin Schneider ◽  
Stephanie Arndt ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Membrane Damage ◽  
Melanoma Cells ◽  
Atmospheric Plasma ◽  
Active Components ◽  
Antitumor Effects ◽  
Cold Atmospheric Plasma ◽  
Viability Analysis ◽  
Cellular Effects ◽  
The Impact

Cold atmospheric plasma (CAP) is partially ionized gas near room temperature with previously reported antitumor effects. Despite extensive research and growing interest in this technology, active components and molecular mechanisms of CAP are not fully understood to date. We used Raman spectroscopy and colorimetric assays to determine elevated nitrite and nitrate levels after treatment with a MiniFlatPlaster CAP device. Previously, we demonstrated CAP-induced acidification. Cellular effects of nitrite and strong extracellular acidification were assessed using live-cell imaging of intracellular Ca2+ levels, cell viability analysis as well as quantification of p21 and DNA damage. We further characterized these observations by analyzing established molecular effects of CAP treatment. A synergistic effect of nitrite and acidification was found, leading to strong cytotoxicity in melanoma cells. Interestingly, protein nitration and membrane damage were absent after treatment with acidified nitrite, thereby challenging their contribution to CAP-induced cytotoxicity. Further, phosphorylation of ERK1/2 was increased after treatment with both acidified nitrite and indirect CAP. This study characterizes the impact of acidified nitrite on melanoma cells and supports the importance of RNS during CAP treatment. Further, it defines and evaluates important molecular mechanisms that are involved in the cancer cell response to CAP.

scholarly journals Acidification is an Essential Process of Cold Atmospheric Plasma and Promotes the Anti-Cancer Effect on Malignant Melanoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 671 ◽  
Author(s):  
Christin Schneider ◽  
Lisa Gebhardt ◽  
Stephanie Arndt ◽  
Sigrid Karrer ◽  
Julia L. Zimmermann ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Melanoma Cells ◽  
Reactive Species ◽  
Atmospheric Plasma ◽  
Protein Nitration ◽  
Cold Atmospheric Plasma ◽  
No Formation ◽  
Anti Cancer ◽  
Acidic Conditions ◽  
The Impact

(1) Background: Cold atmospheric plasma (CAP) is ionized gas near room temperature. The anti-cancer effects of CAP were confirmed for several cancer types and were attributed to CAP-induced reactive species. However, the mode of action of CAP is still not well understood. (2) Methods: Changes in cytoplasmic Ca2+ level after CAP treatment of malignant melanoma cells were analyzed via the intracellular Ca2+ indicator fura-2 AM. CAP-produced reactive species were determined by fluorescence spectroscopic and protein nitration by Western Blot analysis. (3) Results: CAP caused a strong acidification of water and solutions that were buffered with the so-called Good buffers, while phosphate-buffered solutions with higher buffer capacity showed minor pH reductions. The CAP-induced Ca2+ influx in melanoma cells was stronger in acidic pH than in physiological conditions. NO formation that is induced by CAP was dose- and pH-dependent and CAP-treated solutions only caused protein nitration in cells under acidic conditions. (4) Conclusions: We describe the impact of CAP-induced acidification on the anti-cancer effects of CAP. A synergistic effect of CAP-induced ROS, RNS, and acidic conditions affected the intracellular Ca2+ level of melanoma cells. As the microenvironment of tumors is often acidic, further acidification might be one reason for the specific anti-cancer effects of CAP.

scholarly journals Cold Atmospheric Plasma Changes the Amino Acid Composition of Solutions and Influences the Anti-Tumor Effect on Melanoma Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 7886
Author(s):  
Stephanie Arndt ◽  
Fadi Fadil ◽  
Katja Dettmer ◽  
Petra Unger ◽  
Marko Boskovic ◽  
...  
Keyword(s):  
Amino Acids ◽  
Melanoma Cells ◽  
Atmospheric Plasma ◽  
Strong Impact ◽  
Active Components ◽  
Cellular Mechanisms ◽  
Cold Atmospheric Plasma ◽  
Decisive Importance ◽  
Other Substances ◽  
Dose Dependent

Cold Atmospheric Plasma (CAP) is an ionized gas near room temperature. Its anti-tumor effect can be transmitted either by direct treatment or mediated by a plasma-treated solution (PTS), such as treated standard cell culture medium, which contains different amino acids, inorganic salts, vitamins and other substances. Despite extensive research, the active components in PTS and its molecular or cellular mechanisms are not yet fully understood. The purpose of this study was the measurement of the reactive species in PTS and their effect on tumor cells using different plasma modes and treatment durations. The PTS analysis yielded mode- and dose-dependent differences in the production of reactive oxygen and nitrogen species (RONS), and in the decomposition and modification of the amino acids Tyrosine (Tyr) and Tryptophan (Trp). The Trp metabolites Formylkynurenine (FKyn) and Kynurenine (Kyn) were produced in PTS with the 4 kHz (oxygen) mode, inducing apoptosis in Mel Im melanoma cells. Nitrated derivatives of Trp and Tyr were formed in the 8 kHz (nitrogen) mode, elevating the p16 mRNA expression and senescence-associated ß-Galactosidase staining. In conclusion, the plasma mode has a strong impact on the composition of the active components in PTS and affects its anti-tumor mechanism. These findings are of decisive importance for the development of plasma devices and the effectiveness of tumor treatment.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals Cold Atmospheric Plasma induces accumulation of lysosomes and caspase-independent cell death in U373MG glioblastoma multiforme cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gillian E. Conway ◽  
Zhonglei He ◽  
Ana Lacramioara Hutanu ◽  
George Paul Cribaro ◽  
Eline Manaloto ◽  
...  
Keyword(s):  
Cell Death ◽  
Glioblastoma Multiforme ◽  
Plasma Treatment ◽  
Acridine Orange ◽  
Molecular Mechanisms ◽  
Confocal Imaging ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma ◽  
Rapid Accumulation ◽  
Lysosomal Accumulation

Abstract Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death.

Cold atmospheric plasma, a new strategy to induce senescence in melanoma cells

2013 ◽  
Vol 22 (4) ◽  
pp. 284-289 ◽  
Author(s):  
Stephanie Arndt ◽  
Eva Wacker ◽  
Yang-Fang Li ◽  
Tetsuji Shimizu ◽  
Hubertus M. Thomas ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Atmospheric Plasma ◽  
Cold Atmospheric Plasma ◽  
New Strategy

scholarly journals Overview of Cold Atmospheric Plasma in Wounds Treatment

2020 ◽  
Vol 5 (10) ◽  
Keyword(s):  
Wound Healing ◽  
Skin Wound ◽  
Atmospheric Plasma ◽  
Active Components ◽  
Negative Effects ◽  
Skin Wound Healing ◽  
Cold Atmospheric Plasma ◽  
In Vivo Experiments

Cold atmospheric plasma (CAP), a room temperate ionised gas, known as the fourth state of matter is an ionised gas and can be produced from argon, helium, nitrogen, oxygen or air at atmospheric pressure and low temperatures. CAP has become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing have gained huge success both in vitro and in vivo experiments without any known significant negative effects on healthy tissues. The development of CAP devices has led to novel therapeutic strategies in wound healing, tissue regeneration and skin infection management. CAP consists of a mixture of multitude of active components such as charged particles, electric field, UV radiation, and reactive gas species which can act synergistically. CAP has lately been recognized as an alternative approach in medicine for sterilization of wounds by its antiseptic effects and promotion of wound healing by stimulation of cell proliferation and migration of wound related skin cells. With respect to CAP applications in medicine, this review focuses particularly on the potential of CAP and the known molecular basis for this action. We summarize the available literature on the plasma devices developed for wound healing, the current in vivo and in vitro use of CAP, and the mechanism behind it as well as the biosafety issues.

scholarly journals Cold Atmospheric Plasma Cancer Treatment, a Critical Review

2021 ◽  
Vol 11 (16) ◽  
pp. 7757
Author(s):  
Dayun Yan ◽  
Alisa Malyavko ◽  
Qihui Wang ◽  
Li Lin ◽  
Jonathan H. Sherman ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Critical Evaluation ◽  
Atmospheric Plasma ◽  
Physical Factors ◽  
Atmospheric Conditions ◽  
Cold Atmospheric Plasma ◽  
Anti Cancer ◽  
Biological Impacts ◽  
Indirect Treatment

Cold atmospheric plasma (CAP) is an ionized gas, the product of a non-equilibrium discharge at atmospheric conditions. Both chemical and physical factors in CAP have been demonstrated to have unique biological impacts in cancer treatment. From a chemical-based perspective, the anti-cancer efficacy is determined by the cellular sensitivity to reactive species. CAP may also be used as a powerful anti-cancer modality based on its physical factors, mainly EM emission. Here, we delve into three CAP cancer treatment approaches, chemically based direct/indirect treatment and physical-based treatment by discussing their basic principles, features, advantages, and drawbacks. This review does not focus on the molecular mechanisms, which have been widely introduced in previous reviews. Based on these approaches and novel adaptive plasma concepts, we discuss the potential clinical application of CAP cancer treatment using a critical evaluation and forward-looking perspectives.

Sign in / Sign up

Export Citation Format

Share Document