New Treatment Options for Osteosarcoma – Inactivation of Osteosarcoma Cells by Cold Atmospheric Plasma

Gümbel, Denis; Gelbrich, Nadine; Weiß, Martin; Napp, Matthias; Daeschlein, Georg; Sckell, Axel; Ender, Stephan Albrecht; Krämer, Axel; Burchardt, Martin; Stope, Matthias B.

doi:10.21873/anticanres.11178

Cited by 40 publications

(37 citation statements)

References 20 publications

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“…In recent years, CAP have shown lethal in vitro efficiency by direct treatment as well as by plasma-treated cell culture medium in different OS cell lines and by different plasma devices [22,23,[29][30][31]. OS is a heterogeneous disease characterized by presenting different subtypes and high levels of genomic instability [32,33], making it difficult to assess the clinical relevance of new therapeutic options for the different cases.…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 99%

“…From another point of view, up to now, cytotoxicity of CAPs or plasma-activated media in OS cell lines have been investigated only in adherent cell cultures [22,23,[29][30][31]36,37]. This kind of in vitro models provides limited clinically relevant information.…”

Section: Introductionmentioning

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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“…While some studies solely examined the effect of CAP on one cell line, others investigated CAP selectivity between normal and disease cells . Many studies that utilized more than one cell line for CAP‐based experiments used the same fluid for both cell lines (Table S1), while others used different media across different cell lines (Table S1) . In addition, many studies that compared normal and tumor cells used cells from unmatched tissue samples .…”

Section: Introductionmentioning

confidence: 99%

“…Many studies that utilized more than one cell line for CAP‐based experiments used the same fluid for both cell lines (Table S1), while others used different media across different cell lines (Table S1) . In addition, many studies that compared normal and tumor cells used cells from unmatched tissue samples . Furthermore, a majority of previous studies used cells grown on tissue culture plastic (Table S1), where cells primarily rely on polar interactions for adhesion; however, this microenvironment is not representative of the in vivo situation, where cells typically adhere to extracellular matrix (ECM) proteins via integrins .…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of tumor versus normal cell migration and morphology to cold atmospheric plasma‐treated media in varying culture conditions

Pranda

Murugesan

Knoll

et al. 2019

Plasma Processes & Polymers

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Cold atmospheric plasma (CAP) produces reactive oxygen species and reactive nitrogen species, which may disproportionally damage tumor cells, resulting in potentially selective cancer therapy. Here, we compare the effects of two CAP sources, that is, the atmospheric pressure plasma jet and the surface micro discharge, on the selectivity of CAP-treated cell-culture media. CAP-treated media were applied to metastatic breast tumor cells and their normal breast epithelial cell counterparts to assess treatment selectivity, while systematically varying common cell-culture media and cell-matrix binding moieties. We show that media compositions are crucial in a CAP-treated media selectivity, while binding moieties (specifically, collagen I, fibronectin, and poly-D-lysine) play a lesser role. These data have further implications in the translation of CAP to in vivo use. K E Y W O R D Scancer, cell culture, cold plasma, selectivity, therapy

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“…Osteosarcoma, the most common malignant bone tumor, has become the second leading cause of cancer‐related death in the adolescent age group . It is estimated that the incidence rate of osteosarcoma is 4.6‐5.6% for the range 0‐19 years per year per million persons worldwide .…”

Section: Introductionmentioning

confidence: 99%

Mxd1 mediates hypoxia‐induced cisplatin resistance in osteosarcoma cells by repression of the PTEN tumor suppressor gene

Zheng

Dong

et al. 2017

Molecular Carcinogenesis

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Hypoxia-induced chemoresistance remains a major obstacle to treating osteosarcoma effectively. Mxd1, a member of the Myc/Max/Mxd family, was shown to be involved in the development of drug resistance under hypoxia. However, the effect of Mxd1 on hypoxia-induced cisplatin (CDDP) resistance and its mechanism in osteosarcoma have not been fully elucidated. In this study, we demonstrated that HIF-1α-induced Mxd1 contributed to CDDP resistance in hypoxic U-2OS and MG-63 cells. The knockdown of Mxd1 expression elevated PTEN expression at both protein and RNA levels in these hypoxic cells. Using Luciferase reporter and ChIP assays, we confirmed that Mxd1 directly bound to the E-box sites within the PTEN promoter region. We further demonstrated that PTEN knockdown decreased CDDP sensitivity in Mxd1 siRNA-transfected U-2OS and MG-63 cells under hypoxia. Our results also showed that Mxd1 deficiency in hypoxic U-2OS and MG-63 cells lead to inactivation of PI3K/AKT signaling, which is the downstream of PTEN. Furthermore, blockade of PI3K/AKT signal re-sensitized hypoxic U-2OS and MG-63 cells to CDDP. Taken together, these findings suggest that HIF-1α-induced Mxd1 up-regulation suppresses the expression of PTEN under hypoxia, which leads to the activation of PI3K/AKT antiapoptotic and survival pathway. As a result CDDP resistance in osteosarcoma cells is induced.

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New Treatment Options for Osteosarcoma – Inactivation of Osteosarcoma Cells by Cold Atmospheric Plasma

Abstract: Cold atmospheric plasma treatment significantly attenuated cell proliferation in a preclinical in vitro osteosarcoma model. The resulting increase in p53 expression and phospho-activation in combination with characteristic nuclear changes indicate this was through induction of apoptosis.

Cited by 40 publications

References 20 publications

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

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

Sensitivity of tumor versus normal cell migration and morphology to cold atmospheric plasma‐treated media in varying culture conditions

Mxd1 mediates hypoxia‐induced cisplatin resistance in osteosarcoma cells by repression of the PTEN tumor suppressor gene

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