Cold Atmospheric Plasma Versus Cisplatin Against Oral Squamous Cell Carcinoma: A Mitochondrial Targeting Study

Plasma therapy and the study of the effects of cold atmospheric plasma (CAP) on tissues and living cells have been considered by scientific researchers in recent years. CAP is used in the treatment of cancer, but its anti-cancer mechanism has not been fully studied. Therefore, we studied the toxicity effect of CAP by using argon as feed gas and the synergistic effects of CAP with cisplatin on tumor cells and mitochondria isolated from tumor legions of the rat model of oral squamous cell carcinoma (OSCC). For this reason, we determined the possible toxic alterations of CAP on mitochondrial upstream events and activation of caspase-3 as the key major downstream event of apoptosis. Also, the effects of cisplatin (10 µM) as a positive control and its synergistic effects with CAP (IC₅₀ concentration) were investigated. The results showed that CAP reduced mitochondrial dysfunction by reduction in succinate dehydrogenase (SDH) activity. Also, CAP in concentrations of 1200, 2400, and 4800 a.u. has been able to increase the level of reactive oxygen species (ROS), mitochondrial swelling, damage to the mitochondrial membrane, cytochrome c release, and activation of the final mediator of apoptosis (caspase-3) only in the OSCC group. CAP at 4800 a.u concentration had similar effects to cisplatin (10 µM). Synergistic effects between CAP (2400 a.u) and cisplatin (10 µM) have also been reported. Based on all results CAP showed positive and promising results on mitochondrial upstream parameters leading to activation of caspase-3, the final mediator of apoptosis only on OSCC cells and mitochondria without any significant effect on normal cells and mitochondria.