Non-thermal atmospheric plasma induces ROS-independent cell death in U373MG glioma cells and augments the cytotoxicity of temozolomide.

作者: Gillian E Conway , Alan Casey , Vladimir Milosavljevic , Yupeng Liu , Orla Howe

DOI: 10.1038/BJC.2016.12

关键词: Cell cultureCytotoxicityFlow cytometryApoptosisHeLaViability assayBiologyCytotoxic T cellCancer researchCancer cellPharmacology

摘要: Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported the literature. The aim of this study was determine whether against NTAP could be overcome using human glioma cell line U373MG. generated Dielectric Barrier Device (DBD) system with maximum output 120 kV at 50 Hz. viability U373MG GBM cells HeLa cervical carcinoma determined morphology, flow cytometry assays. Fluorescent probes inhibitors were used mechanisms exposed field. Combinational therapy temozolomide (TMZ) multi-dose treatments explored as NTAP. decreased dose (time)-dependent manner. shown resistant treatment when compared cells, levels intracellular reactive oxygen (ROS) quantified much lower than following exposure Reactive inhibitor N-acetyl cysteine (NAC) only alleviated effects not relatively NTAP-resistant Longer exposures induced death independent ROS, JNK caspases relative combination low concentrations chemotherapy TMZ or multiple doses. For very first time, we report induces ROS-, JNK- caspase-independent mechanism greatly enhanced doses TMZ. Further refinement technology may facilitate localised activation new existing chemotherapeutic regimens.

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