Cold atmospheric helium plasma causes synergistic enhancement in cell death with hyperthermia and an additive enhancement with radiation

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.

Comparison of Three Radio-Frequency Discharge Modes on the Treatment of Breast Cancer Cells in Vitro

“…In our experiment, the same amount of DNA damages is observed using any dis- charge mode (at a dose for which proliferation is similarly affected) or positive control (8 Gy of radiation therapy). Despite the generally accepted difference in the underlying physical mechanisms leading to cell death by plasma and radiation therapy (exogenous production of extracellular vs. intracellular RONS [42]), in the present experimental setup, it is possible that irradiation of cells in suspension with high energy photons (Caesium-137) relies on the same mechanisms as plasma treatment. As most of the irradiated volume (> 99%) is occupied by culture medium, the principal effect of radiation therapy might be related to radiation energy deposited within the liquid (as opposed to within cells).…”

Small size gold nanoparticles enhance apoptosis-induced by cold atmospheric plasma via depletion of intracellular GSH and modification of oxidative stress

“…To address this problem, a multimodality strategy was recently adopted by combining nanoparticles carrying drugs with CAP. Previously, we showed the synergism in He-CAP induced apoptosis upon exposure to hyperthermia and sulfasalazine 17,18 . Fig.…”

Pyruvate Plays a Main Role in the Antitumoral Selectivity of Cold Atmospheric Plasma in Osteosarcoma

“…The species measured in this work are an example of some of the many RONS that may be formed in CAP treated liquids. Other species that we could assume to be present in our PAM are NO 3 − which is often quantified in saline solutions 56,57 , or cell culture media 42 , *OH that was observed in aqueous solution by electron paramagnetic resonance (EPR) 58 , or ONOO − which is known also to be of importance in biological processes but not straightforward to measure in liquids.…”