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.