Nonthermal plasma specifically kills oral squamous cell carcinoma cells in a catalytic Fe(II)dependent manner

Oral cancer accounts for ~2% of all cancers worldwide, and ther apeutic intervention is closely associated with quality of life. Here, we evaluated the effects of nonthermal plasma on oral squa mous cell carcinoma cells with special reference to catalytic Fe(II). Nonthermal plasma exerted a specific killing effect on oral squa mous cell carcinoma cells in comparison to fibroblasts. Furthermore, the effect was dependent on the amounts of catalytic Fe(II), pres ent especially in lysosomes. After nonthermal plasma application, lipid peroxidation occurred and peroxides and mitochondrial super oxide were generated. Cancer cell death by nonthermal plasma was promoted dosedependently by prior application of ferric ammonium citrate and prevented by desferrioxamine, suggesting the association of ferroptosis. Potential involvement of apoptosis was also observed with positive terminal deoxynucleaotidyl transferasemediated dUTP nick end labeling and annexin V results. Nonthermal plasma exposure significantly suppressed the migratory, invasive and colonyforming abilities of squamous cell carcinoma cells. The oral cavity is easily observable; therefore, nonthermal plasma can be directly applied to the oral cavity to kill oral squamous cell carcinoma without damaging fibroblasts. In conclusion, nonthermal plasma treatment is a potential therapeutic option for oral cancer.