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Reduction of Human Glioblastoma Spheroids Using Cold Atmospheric Plasma: The Combined Effect of Short- and Long-Lived Reactive Species

1
PLASMANT, Chemistry Department, University of Antwerp, 2610 Antwerp, Belgium
2
Solid Tumor Immunology Group, Center for Oncological Research, University of Antwerp, 2610 Antwerp, Belgium
3
Protein Chemistry, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp, 2610 Antwerp, Belgium
*
Author to whom correspondence should be addressed.
Cancers 2018, 10(11), 394; https://doi.org/10.3390/cancers10110394
Received: 20 September 2018 / Revised: 9 October 2018 / Accepted: 19 October 2018 / Published: 23 October 2018
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
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Abstract

Cold atmospheric plasma (CAP) is a promising technology against multiple types of cancer. However, the current findings on the effect of CAP on two-dimensional glioblastoma cultures do not consider the role of the tumour microenvironment. The aim of this study was to determine the ability of CAP to reduce and control glioblastoma spheroid tumours in vitro. Three-dimensional glioblastoma spheroid tumours (U87-Red, U251-Red) were consecutively treated directly and indirectly with a CAP using dry He, He + 5% H2O or He + 20% H2O. The cytotoxicity and spheroid shrinkage were monitored using live imaging. The reactive oxygen and nitrogen species produced in phosphate buffered saline (PBS) were measured by electron paramagnetic resonance (EPR) and colourimetry. Cell migration was also assessed. Our results demonstrate that consecutive CAP treatments (He + 20% H2O) substantially shrank U87-Red spheroids and to a lesser degree, U251-Red spheroids. The cytotoxic effect was due to the short- and long-lived species delivered by CAP: they inhibited spheroid growth, reduced cell migration and decreased proliferation in CAP-treated spheroids. Direct treatments were more effective than indirect treatments, suggesting the importance of CAP-generated, short-lived species for the growth inhibition and cell cytotoxicity of solid glioblastoma tumours. We concluded that CAP treatment can effectively reduce glioblastoma tumour size and restrict cell migration, thus demonstrating the potential of CAP therapies for glioblastoma. View Full-Text
Keywords: cancer; cold atmospheric plasma (CAP); spheroid shrinkage; cytotoxicity; tumour reduction; glioblastoma; short-lived reactive species; cell migration; proliferation cancer; cold atmospheric plasma (CAP); spheroid shrinkage; cytotoxicity; tumour reduction; glioblastoma; short-lived reactive species; cell migration; proliferation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Privat-Maldonado, A.; Gorbanev, Y.; Dewilde, S.; Smits, E.; Bogaerts, A. Reduction of Human Glioblastoma Spheroids Using Cold Atmospheric Plasma: The Combined Effect of Short- and Long-Lived Reactive Species. Cancers 2018, 10, 394.

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