Abstract

Cold atmospheric plasmas (CAPs) have been proposed as a novel therapeutic method for its anti-cancer potential. However, its biological effects in combination with other physical modalities remain elusive. Therefore, this study examined the effects of cold atmospheric helium plasma (He-CAP) in combination with hyperthermia (HT) 42 °C or radiation 5 Gy. Synergistic enhancement in the cell death with HT and an additive enhancement with radiation were observed following He-CAP treatment. The synergistic effects were accompanied by increased intracellular reactive oxygen species (ROS) production. Hydrogen peroxide (H2O2) and superoxide (O2•–) generation was increased immediately after He-CAP treatment, but fails to initiate cell death process. Interestingly, at late hour’s He-CAP-induced O2•– generation subsides, however the combined treatment showed sustained increased intracellular O2•– level, and enhanced cell death than either treatment alone. He-CAP caused marked induction of ROS in the aqueous medium, but He-CAP-induced ROS seems insufficient or not completely incorporated intra-cellularly to activate cell death machinery. The observed synergistic effects were due to the HT effects on membrane fluidity which facilitate the incorporation of He-CAP-induced ROS into the cells, thus results in the enhanced cancer cell death following combined treatment. These findings would be helpful when establishing a therapeutic strategy for CAP in combination with HT or radiation.

Highlights

  • Cancer is still the leading cause of deaths worldwide, with increasing incidence because of changing lifestyle and increased exposure to carcinogens[1]

  • The results showed that the percentage of apoptotic cells induced by He-Cold atmospheric plasmas (CAPs) and HT treatment alone were less than 10%, when cells were exposed to combined treatment; it was increased to 22.5% and 45.5% with 120 s and 180 s, respectively

  • The efficacy of combined treatment was evaluated at longer time period; cell survival was assayed by CCk-8 following combined treatment at 24 h, as shown in Supplementary Fig. S1A, the cell survival after HT treatment alone was 94% ± 7.8, with combined treatment it declined to 66% ± 6.7 and 16% ± 2.0, with helium cold atmospheric plasma (He-CAP) 120 s and 180 s, respectively, showing synergistic enhancement in the cell death

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Summary

Introduction

Cancer is still the leading cause of deaths worldwide, with increasing incidence because of changing lifestyle and increased exposure to carcinogens[1]. The effects of CAP on other physical modalities such as hyperthermia (HT) and radiation has not been studied yet Both HT and radiation are known anti-cancer therapies, the impact of HT and radiation alone or in combination have been well documented[20]. Both therapies have been associated with un-intended effects because of exposure to high temperatures and radiation doses. In this study the effects of helium cold atmospheric plasma (He-CAP) were investigated on HT 42 °C or low dose radiation 5 Gy and described the molecular insight involved in the combined treatment using human myelomonocytic lymphoma U937 cells

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