Abstract
New approaches in oncotherapy rely on the combination of different treatments to enhance the efficacy of established monotherapies. Pulsed electric fields (PEFs) are an established method (electrochemotherapy) for enhancing cellular drug uptake while cold physical plasma is an emerging and promising anticancer technology. This study aimed to combine both technologies to elucidate their cytotoxic potential as well as the underlying mechanisms of the effects observed. An electric field generator (0.9–1.0 kV/cm and 100-μs pulse duration) and an atmospheric pressure argon plasma jet were employed for the treatment of lymphoma cell lines as a model system. PEF but not plasma treatment induced cell membrane permeabilization. Additive cytotoxicity was observed for the metabolic activity and viability of the cells while the sequence of treatment in the combination played only a minor role. Intriguingly, a parallel combination was more effective compared to a 15-min pause between both treatment regimens. A combination effect was also found for lipid peroxidation; however, none could be observed in the cytosolic and mitochondrial reactive oxygen species (ROS) production. The supplementation with either antioxidant, a pan-caspase-inhibitor or a ferroptosis inhibitor, all partially rescued lymphoma cells from terminal cell death, which contributes to the mechanistic understanding of this combination treatment.
Highlights
Cold physical plasma applied in the field of plasma medicine is an ionized gas close to body temperature [1]
Pulsed electric fields (PEFs) (Figure 1C) and plasma (Figure 1D) treatment (Table 1). This included plasma treatment followed by PEF treatment and vice versa
PEF but not Plasma Treatment Led to Cell Membrane Permeabilization
Summary
Cold physical plasma applied in the field of plasma medicine is an ionized gas close to body temperature [1]. Plasmas are multi-component systems generating UV radiation, visible light, electromagnetic fields, thermal radiation, electrons and ions, and reactive oxygen species (ROS) and reactive nitrogen species (RNS) [2]. The latter play a crucial role in mediating the plasma effects in cells [3,4,5] by mediating oxidative modifications [6,7,8] to induce signaling pathways [9,10,11]. The exact mechanism of plasma-induced apoptosis seems to be cell line dependent, varying from A range of cellular responses have been found, including apoptosis, growth inhibition, cell cycle arrest, as well as cytoskeletal and mitochondrial damage [18,19,20].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
