Abstract
The application of cold atmospheric plasma (CAP) in cancer therapy could be one of the new anticancer strategies. In the current work, we used cold atmospheric plasma jet for the treatment of cultured cells and mice. We showed that CAP induced the death of MX−7 mouse rhabdomyosarcoma cells with the hallmarks of immunogenic cell death (ICD): calreticulin and heat shock protein 70 (HSP70) externalization and high-mobility group box 1 protein (HMGB1) release. The intensity of HMGB1 release after the CAP treatment correlated directly with the basal extracellular HMGB1 level. Releasing from dying cells, HMGB1 can act as a proinflammatory cytokine. Our in vivo study demonstrated that cold atmospheric plasma induces a short-term two-times increase in serum HMGB1 level only in tumor-bearing mice with no effect in healthy mice. These findings support our hypothesis that CAP-dependent HMGB1 release from dying cancer cells can change the serum HMGB1 level. At the same time, we showed a weak cytokine response to CAP irradiation in healthy mice that can characterize CAP as an immune-safety physical antitumor approach.
Highlights
While a great number of anticancer therapeutics have been developed, their efficiency is still limited resulting in a high rate of cancer-associated deaths
Yoon and co-authors have shown that cold atmospheric plasma (CAP) induced the expression of high-mobility group box 1 protein (HMGB1) in cancer cells [11]. These findings indicated that CAP can change the intra- and extra-cellular level of HMGB1
Launching the ‘hypoxia’ leads to changes in the tumor cell proteome as wellTahsegceenlolumlairc riendstoaxbeilnitvyir[o1n8m]. ent regulates the temporal functions of HMGB1
Summary
While a great number of anticancer therapeutics have been developed, their efficiency is still limited resulting in a high rate of cancer-associated deaths. Physical approaches of tumor irradiation were tested in various cancers. The application of cold atmospheric plasma (CAP) in cancer therapy solo or in combination with chemo- and immunotherapeutics could be one of the new anticancer strategies [1]. To reinforce CAP potential against cancers, it was combined with modern immunotherapeutic drugs, including checkpoint inhibitors, and this approach resulted in tumor suppression and prolonged survival [2]. Being generated at room temperature, CAP minimizes a risk of the thermal damage of irradiated tissue [3]. The generation of non-thermal atmospheric pressure plasma depends on the discharge geometry, the setup of operating gas or gas mixture flow and the methods of gas excitation. The discharge device is a dielectric tube in which the flow of operating gas is organized and where the low temperature plasma is generated [4]
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