Cold atmospheric plasma (CAP) is an intensively-studied approach for the treatment of malignant neoplasms. Various active oxygen and nitrogen compounds are believed to be the main cytotoxic effectors on biotargets; however, the comprehensive mechanism of CAP interaction with living cells and tissues remains elusive. In this study, we experimentally determined the optimal discharge regime (or semi-selective regime) for the direct CAP jet treatment of cancer cells, under which lung adenocarcinoma A549, A427 and NCI-H23 cells demonstrated substantial suppression of viability, coupled with a weak viability decrease of healthy lung fibroblasts Wi-38 and MRC-5. The death of CAP-exposed cancer and healthy cells under semi-selective conditions was caspase-dependent. We showed that there was an accumulation of lysosomes in the treated cells. The increased activity of lysosomal protease Cathepsin D, the transcriptional upregulation of autophagy-related MAPLC3B gene in cancer cells and the changes in autophagy-related proteins may have indicated the activation of autophagy. The addition of the autophagy inhibitor chloroquine (CQ) after the CAP jet treatment increased the death of A549 cancer cells in a synergistic manner and showed a low effect on the viability of CAP-treated Wi-38 cells. Downregulation of Drp1 mitochondrial protein and upregulation of PINK1 protein in CAP + CQ treated cells indicated that CQ increased the CAP-dependent destabilization of mitochondria. We concluded that CAP weakly activated pro-survival autophagy in irradiated cells, and CQ promoted CAP-dependent cell death due to the destabilization of autophagosomes formation and mitochondria homeostasis. To summarize, the combination of CAP treatment with CQ could be useful for the development of cold plasma-based antitumor approaches for clinical application.
Low-temperature plasma jets at atmospheric pressure generated by sinusoidal and positive pulsed voltages interact differently with the treated surface. In the experiment and in numerical simulations, we compare the operating modes of helium plasma jets for these types of operating voltages. The discharge current on the treated surface over time and the surface heating are studied for different discharge parameters acceptable for anticancer therapy. The intensity of the emission spectrum is analyzed to improve the effectiveness of the plasma jet. Surface heating is controlled in order to meet the safety conditions of plasma exposure to biological objects. For the case of pulsed voltage the effect of voltage pulse duration on the intensity of plasma-surface interaction is discussed. The results on cancer cells A549 and MCF-7 demonstrate the high efficiency of the cold plasma jet generated at found optimal modes.
The effect of placing a grounded substrate beneath the dielectric target or cancer cells during exposure to the cold atmospheric plasma jet is studied in the experiments and in fluid model simulations for the discharge parameters typical for the medical applications. It is shown that the dynamics of streamers generated in each positive cycle of ac voltage depends on the grounded substrate position. The streamers approach the target more often if the grounded substrate is beneath the target, that provides more intensive plasma-target interaction. In this case, the measured spectrum of plasma jet emission near the target demonstrates much higher intensity compared to an electrically isolated target case. The calculated and measured discharge currents with time demonstrate a mismatch of frequencies of the ac voltage and current over the target. The effect of relocation of the grounded substrate on the viability of plasma-irradiated cancer cells is analyzed. The viability of A431 human skin carcinoma and MX7 mouse rhabdomyosarcoma cells treated by cold atmospheric plasma jet is measured with MTT assay 24 hours after. The results show an enhanced suppression of the cell viability with using the grounded substrate for both cell lines. Achieving effective death of tumor cells with a shorter irradiation time can be considered an advantage of using a grounded electrode.
Cold atmospheric plasma (CAP) jet generated by the plasma source at 2-6 kV ac voltages with frequencies of 10-50 kHz demonstrate the different modes of operation. Depending on the voltage frequency and amplitude, some streamers in the plasma jet are short and decay before they approach the treated surface. In this case, the effect on the viability of cancer cells when exposed to CAP jet strongly depends on the mode of operation of the discharge or, in other words, on how many times the streamers hit the bio-target during the treatment. The effect on different modes on cancer cells A549 viability is reported.
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