Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells

Azzariti, Amalia; Iacobazzi, Rosa Maria; Fonte, R.; Porcelli, Letizia; Gristina, Roberto; Favia, Pietro; Fracassi, Francesco; Trizio, Ilaria; Silvestris, Nicola; Guida, Gabriella; Tommasi, Stefania; Sardella, Eloisa

doi:10.1038/s41598-019-40637-z

Cited by 116 publications

(89 citation statements)

References 83 publications

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“…Within the tumor microenvironment, they recognize tumor antigens and lyse the target cells, helping the body to fight cancer using its endogenous weapons provided by the immune system. Using direct plasma treatment or plasma-conditioned liquids, ICD has been observed in vitro in a number of tumor cell types including, for instance, pancreatic cancer, colorectal cancer, lung cancer, and malignant melanoma [99,[131][132][133][134][135][136][137][138][139][140]. Due to the extensive poly-pragmasia of plasma sources used in the field of plasma medicine, the central mechanisms underlying plasma-induced ICD have not been commonly unraveled.…”

Section: Induction Of An Immune Response Through Cap Treatmentmentioning

confidence: 99%

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Semmler

Bekeschus

Schäfer

et al. 2020

Cancers

140

122

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Recently, the potential use of cold atmospheric pressure plasma (CAP) in cancer treatment has gained increasing interest. Especially the enhanced selective killing of tumor cells compared to normal cells has prompted researchers to elucidate the molecular mechanisms for the efficacy of CAP in cancer treatment. This review summarizes the current understanding of how CAP triggers intracellular pathways that induce growth inhibition or cell death. We discuss what factors may contribute to the potential selectivity of CAP towards cancer cells compared to their non-malignant counterparts. Furthermore, the potential of CAP to trigger an immune response is briefly discussed. Finally, this overview demonstrates how these concepts bear first fruits in clinical applications applying CAP treatment in head and neck squamous cell cancer as well as actinic keratosis. Although significant progress towards understanding the underlying mechanisms regarding the efficacy of CAP in cancer treatment has been made, much still needs to be done with respect to different treatment conditions and comparison of malignant and non-malignant cells of the same cell type and same donor. Furthermore, clinical pilot studies and the assessment of systemic effects will be of tremendous importance towards bringing this innovative technology into clinical practice.

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Section: Induction Of An Immune Response Through Cap Treatmentmentioning

confidence: 99%

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Semmler

Bekeschus

Schäfer

et al. 2020

Cancers

140

122

View full text Add to dashboard Cite

show abstract

“…Cold atmospheric plasma (referred as 'plasma') is described as a room temperature ionized gas generated at atmospheric pressure. Plasma generates reactive oxygen and nitrogen species (RONS), which, once applied to cancer cells, have the potential to induce DNA damages leading to cell apoptosis [1] or cause immunogenic cell death [2][3][4]. More importantly, cancer cells appear to be more sensitive to plasma than healthy cells [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Potential of Two Plasma-Activated Liquids: Implication of Long-Lived Reactive Oxygen and Nitrogen Species

Griseti

Merbahi

Golzio

2020

Cancers

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Cold atmospheric plasma-exposed culture medium may efficiently kill cancer cells in vitro. Due to the complexity of the medium obtained after plasma exposure, less complex physiological liquids, such as saline solutions and saline buffers, are gathering momentum. Among the plethora of reactive oxygen and nitrogen species (RONS) that are produced in these plasma-activated liquids, hydrogen peroxide, nitrite and nitrate appear to be mainly responsible for cytotoxic and genotoxic effects. Here, we evaluated the anti-cancer potential of plasma-activated phosphate-buffered saline (P-A PBS) and sodium chloride 0.9% (P-A NaCl), using a three-dimensional tumor model. Two epithelial cancer cell lines were used to evaluate cellular effects of either P-A PBS or P-A NaCl. Human colorectal cancer cells HCT 116 and human ovarian carcinoma, SKOV-3 were used to investigate the manner by which different cell types respond to different plasma-activated liquids treatments. Our investigations indicate that P-A PBS is more efficient than P-A NaCl mainly because RONS are produced in larger quantities. Indeed, we show that the cytotoxicity of these liquids directly correlates with the concentration of hydrogen peroxide and nitrite. Moreover, P-A PBS induced a faster-occurring and more pronounced cell death, which arose within deeper layers of the 3D multicellular spheroid models.Hydrogen peroxide (H 2 O 2 ), nitrite (NO 2 − ) and nitrate (NO 3 − ) have been described as the three main RONS responsible for plasma-exposed solutions antitumor effects [15], as other short-lived species are quenched very rapidly [16]. The complex process that drives RONS diffusion/penetration within cells and the subsequent chemical reactions remain unclear. More recently, a chemical model has been proposed by Bauer, speculating that an auto-amplificatory response of tumor cells, caused by singlet oxygen, occurs after being in direct contact with plasma or with plasma-activated solutions, leading to subsequent reaction and self-perpetuation of toxicity [17].Most of the studies focusing on plasma-activated culture media for cancer cell treatment show that the contents of these solutions play a key role in their anticancer effects. Indeed, the presence of amino acids, fetal bovine serum, and pyruvate have an impact on the final composition of the plasma-activated solutions and the rate of RONS produced [18,19]. Therefore, there is now a growing interest in switching to physiological and stable solutions, such as water, physiological buffers, and saline solutions, in order to have better control over the species generated after plasma exposure, with the objective of translating it to in vivo applications. A comparative study with six different physiological liquids has been reported recently and referenced their effects in vitro on 2D plated CT26 colorectal cancer cells in terms of cell death, metabolic activity, and cell morphology and displacement [20].SKOV-3 and HCT-116 are both epithelial cancer cell lines. In a recent study, we demonstrated that a plasma-...

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“…In addition, the in vivo reduction of subcutaneously implanted tumors in nude mice from the ovary, glioma cells, and bladder cancer cells exposed to CAP or plasma‐activated liquid has also been demonstrated. And plasma‐activated liquid is expected to be an alternative therapy pathway for the deeper cancers . For clinical research, CAP has been verified as a safe and effective clinical intervention to treat head and neck cancer .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the anticancer effects induced by cold atmospheric plasma in 2D and 3D cell‐culture models

Zhang

Liu

et al. 2019

Plasma Processes & Polymers

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The biological characteristics of three‐dimensional (3D) tumors cannot be adequately represented through two‐dimensional (2D) cell cultures. Here, to acquire more precise information about plasma–tumor interactions, the plasma‐induced cytotoxicity was tested in both 2D cell culture and 3D tumor‐spheroid culture. The results indicated that the toxic effects were markedly reduced in 3D cancer cells compared with 2D cells. We found that reactive oxygen and nitrogen species can penetrate through the entire depth of 3D tumor spheroid, but local apoptosis was observed only on the outermost layer. The permeation depth of plasma‐generated reactive species was then tracked in 3D tumor spheroids. We hypothesized that plasma‐induced apoptosis within a tumor depends on the “deep” delivery of H2O2, NO2−, and NO3− rather than O2−, OH•, and ONOOH/ONOO−.

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Plasma-activated medium triggers cell death and the presentation of immune activating danger signals in melanoma and pancreatic cancer cells

Cited by 116 publications

References 83 publications

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Molecular Mechanisms of the Efficacy of Cold Atmospheric Pressure Plasma (CAP) in Cancer Treatment

Anti-Cancer Potential of Two Plasma-Activated Liquids: Implication of Long-Lived Reactive Oxygen and Nitrogen Species

Evaluation of the anticancer effects induced by cold atmospheric plasma in 2D and 3D cell‐culture models

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