Abstract
Cold atmospheric plasma (CAP) technology, a relatively novel technique mainly investigated as a stand-alone cancer treatment method in vivo and in vitro, is being proposed for application in conjunction with chemotherapy. In this study, we explore whether CAP, an ionized gas produced in laboratory settings and that operates at near room temperature, can enhance Temozolomide (TMZ) cytotoxicity on a glioblastoma cell line (U87MG). Temozolomide is the first line of treatment for glioblastoma, one of the most aggressive brain tumors that remains incurable despite advancements with treatment modalities. The cellular response to a single CAP treatment followed by three treatments with TMZ was monitored with a cell viability assay. According to the cell viability results, CAP treatment successfully augmented the effect of a cytotoxic TMZ dose (50 μM) and further restored the effect of a non-cytotoxic TMZ dose (10 μM). Application of CAP in conjunction TMZ increased DNA damage measured by the phosphorylation of H2AX and induced G2/M cell cycle arrest. These findings were supported by additional data indicating reduced cell migration and increased αvβ3 and αvβ5 cell surface integrin expression as a result of combined CAP–TMZ treatment. The data presented in this study serve as evidence that CAP technology can be a suitable candidate for combination therapy with existing chemotherapeutic drugs. CAP can also be investigated in future studies for sensitizing glioblastoma cells to TMZ and other drugs available in the market.
Highlights
Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant brain tumor among adults
Administration of TMZ has been reported to exert an effect in the expression levels of cell surface receptors, known as integrins, that are responsible for cancer cell migration, survival and angiogenesis16. αvβ[3] and αvβ[5] are two of the main integrins positively associated with cell migration and drug resistance in g lioblastoma[17,18]
Combined Cold atmospheric plasma (CAP)–TMZ treatment causes a reduction in cell viability compared to TMZ
Summary
Glioblastoma multiforme (GBM) is the most common and aggressive type of malignant brain tumor among adults. CAP can be artificially produced in laboratory settings by applying a high alternating electric current through a gas which results in a plasma glow discharge This type of plasma generation only thermalizes the electrons and not the heavier ions and neutral species, the overall plasma system remains near room temperature, making it ideal for biomedical applications as it operates under the threshold of thermal damage. Investigating the molecular anticancer mechanisms in combined CAP–TMZ treatment is significant in improving our understanding of the role of CAP therapy In this investigation we evaluated the effect of CAP applied in conjunction with TMZ on the treatment of U87MG glioblastoma cells. We assessed whether CAP could enhance the effect of a cytotoxic TMZ dose, and described treatment outcomes in terms of cell viability, cell cycle distribution, DNA damage, cell migration and αv, αvβ[3], and αvβ[5] cell surface integrin expression
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