Non-Thermal Plasma As An Innovative Anticancer Strategy On Leukemia Models

Abstract

Antitumor chemotherapy is often hampered by the low therapeutic index of most anticancer drugs and the development of chemoresistance. Furthermore, in leukemia incidence and death rates in patients are really close to each other, when compared to other kind of tumors; pointing out that efficacy of anticancer therapy is suboptimal. Thus, there is a continuous need for new intervention strategies, endowed with a better pharmaco-toxicological profile. Cold atmospheric plasma (CAP) has gained interest as a promising anticancer strategy and earlier studies demonstrated the “non-aggressive” nature of CAP [1]. Several lines of evidence showed that the anticancer activity of CAP mainly depends on the increase in oxidative and nitrosative stress that leads to tumor cell death [2]. However, mechanisms of CAP-cell interaction are not yet completely understood. In this context, the aim of this work is to unravel CAP anticancer effects on in vitro and ex vivo leukemia models achieved within the Italian national project “Scientific Independence for young Researchers” (SIR), that brings together a multidisciplinary team in the areas of Engineering, Pharmacology and Oncohematology. The cytotoxic impact of different CAP treatments performed by means of two plasma sources, a nanosecond pulsed dielectric barrier discharge (DBD) [3,4] and a microsecond pulsed DBD jet (Fig.1), on T-lymphoblastic cell lines was investigated. In particular, we analyzed apoptotic and/or necrotic events, cell-cycle progression, levels of proteins involved in the regulation of apoptosis correlated to reactive oxygen and nitrogen species (RONS) induced in culture medium by CAP treatment. Due to the key role of RONS in the biological effects of CAPs, its genotoxic potential was assessed. Furthermore, some preliminary results indicate that CAPs can induce cytotoxic effects also on leukemia cells cultivated in hypoxia, which plays a critical role in promoting chemoresistance. Taken together, the results we obtained contribute to understand the pharmaco-toxicological potential of CAP, thus making the basis to further investigate its anticancer properties.

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Figure 1: Nanosecond pulsed DBD on a grounded plate (right) and microsecond pulsed DBD jet (left).