Cold atmospheric helium plasma induces apoptosis by increasing intracellular reactive oxygen and nitrogen species

Cold atmospheric pressure plasma (CAPP) has been proposed as a novel method for anticancer therapy. This field gained much interest in the last decade, with biological applications such as wound healing, bacterial sterilization, and cancer treatment. However, the mechanism at the basis of plasma-cell interaction remains unclear. Here, we studied the effect of helium (He) gas CAPP on oral squamous cell carcinoma (OSCC) in vitro. CAPP treatment was performed under different treatment time conditions: 1, 3, and 5 min. Results showed that CAPP treatment induces cell death in OSCC cells in a dose-dependent manner. He-CAPP also induces cell death and G1 cell cycle arrest associated with the ATM/P53 pathway. Furthermore, CAPP activates the mitochondria-mediated apoptosis pathway by enhancing Bax expression and of the Bcl-2 protein suppression. Hydrogen peroxide (H₂ O₂) generation increased immediately after He plasma treatment but reached basal level after 3 h. Further studies showed that CAPP increases intracellular ROS and RNS and reverts after a long period of plasma treatment. Taken together, these results indicated that He-CAPP induces cell death and cell cycle arrest and activates mitochondria-mediated apoptosis by increasing intracellular reactive oxygen and nitrogen species (ROS and RNS) in OSCC cells. Our study provides deep understanding of He-CAPP’s effect on OSCC cells. We suggest that CAPP could be a potential therapeutic and clinical research tool for oral cancer treatment.