The Specific Vulnerabilities of Cancer Cells to the Cold Atmospheric Plasma-Stimulated Solutions

Yan, Dayun; Cui, Haitao; Zhu, Wei; Nourmohammadi, Niki; Milberg, Julian; Zhang, Lijie Grace; Sherman, Jonathan H.

doi:10.1038/s41598-017-04770-x

Cited by 91 publications

(92 citation statements)

References 64 publications

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“…Xiang L et al reported that PAM could selectively reduce the cell viability of triple negative breast cancer cells 23 . Cell death was also induced by treatment with PAM in other types of cancers, including pancreatic cancer, glioblastoma, squamous head and neck cancer, and melanoma [24][25][26] . These authors presumed that the underlying mechanism of cell death was related to increased apoptosis through the accumulation of intracellular reactive oxygen species (ROS).…”

Section: Discussionmentioning

confidence: 99%

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

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the biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (pAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro.Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. in addition, we evaluated the molecular mechanism of pAM activity and found that the mtoR pathway was inactivated by pAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that pAM decreases the viability of endometrial cancer cells along with alteration of the mtoR pathway, which is critical for cancer cell viability. collectively, our data suggest that pAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.Endometrial cancer is the most common gynecologic malignancy in Japan, with an estimated 13,600 new cases diagnosed in 2015 1 . The incidence of new cases is believed to have increased over the last few decades due to increased levels of obesity, hypertension, and diabetes mellitus, particularly in South Africa and several Asian countries including Japan 1,2 . Although the majority of endometrial cancer patients are diagnosed in the early stage and outcomes are generally favorable because of the typical symptom of irregular vaginal bleeding in women of menopausal age, the prognoses of patients in advanced stages not amenable to localized therapies remain poor 1 . Indeed, a frequent pattern of progression and recurrence is peritoneal metastasis, which is often resistant to systemic chemotherapy 3 . In addition, cytotoxic agents for endometrial cancer are relatively limited compared with other gynecologic malignancies. Thus, there is an increasing demand for novel approaches to peritoneal dissemination.For the past decade, nonequilibrium atmospheric pressure plasma (NEAPP) has been studied for its clinical applications such as sterilization, wound healing, and cancer therapy 4-6 . NEAPP represents a partially ionized gas with energy mainly accumulated as free electrons 7 . Recent studies have revealed that in addition to the direct irradiation of NEAPP to bacteria or tissues, indirect plasma treatment with plasma-activated medium (PAM) and plasma-activated lactate (PAL), which are activated by NEAPP, exhibit anti-tumor activity in several types of cancer, including ovarian, pancreatic, colorectal and gastric cancers 4,8-13 . The molecular mechanism of the anti-tumor effects triggered by PAM have been investigat...

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Section: Discussionmentioning

confidence: 99%

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Yoshikawa

Liu

Nakamura

et al. 2020

Sci Rep

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“…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]. This selectivity could be explained by the RONS-induced stress tolerance threshold, which is higher in normal cells than cancer cells, due to their increased production of reactive oxygen species [10][11][12].…”

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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“…They found that these two amino acids in plasma‐treated PBS are highly effective in consuming the plasma‐generated hydrogen peroxide and confirmed this also for the cell culture medium DMEM . Furthermore, the treatment of cells with N ‐acetyl cysteine could prevent cell injury by CAP …”

Section: Resultsmentioning

confidence: 71%

Pyruvate as a cell‐protective agent during cold atmospheric plasma treatment in vitro: Impact on basic research for selective killing of tumor cells

Bergemann

Rebl

Otto

et al. 2019

Plasma Processes & Polymers

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Promising investigations on the selective killing of tumor cells were reported using cold atmospheric pressure plasma (CAP) in vitro. Pyruvate, a supplement in cell culture media, could protect cells against the action of reactive oxygen species. Here, we provide an overview of the in vitro studies concerning the selective killing of tumor cells by CAP with special emphasis on pyruvate concentration in the cell culture media. Several former studies were performed in media with different pyruvate content. Our cell experiments confirmed that pyruvate mitigates the action of the plasma‐activated medium on cells. Therefore, future in vitro studies should be done in media with similar pyruvate content.

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The Specific Vulnerabilities of Cancer Cells to the Cold Atmospheric Plasma-Stimulated Solutions

Cited by 91 publications

References 64 publications

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

Plasma-activated medium promotes autophagic cell death along with alteration of the mTOR pathway

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

Pyruvate as a cell‐protective agent during cold atmospheric plasma treatment in vitro: Impact on basic research for selective killing of tumor cells

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