Ferroptosis induced by plasma-activated Ringer's lactate solution prevents oral cancer progression.

Abstract

This study aimed to investigate the effect of plasma-activated Ringer's lactate solution (PAL) on oral squamous cell carcinoma (OSCC) cells and carcinogenic processes with a particular focus on iron and collagenous matrix formation. We used three OSCC cell lines, one keratinocyte cell line, and two fibroblast lines, and cell viability assays, immunoblotting, flow cytometry, and transmission electron microscopy were performed to evaluate the effect and type of cell death. The effect of PAL treatment on lysyl oxidase (LOX) expression was investigated invitro and invivo. Tamoxifen-inducible Mob1a/b double-knockout mice were used for the invivo experiment. PAL killed OSCC cells more effectively than the control nontumorous cells and suppressed cell migration and invasion. Ferroptosis occurred and the protein level of LOX was downregulated in cancer cells invitro and invivo. Additionally, PAL improved the survival rate of mice and suppressed collagenous matrix formation. We demonstrated that PAL specifically kills OSCC cells and that ferroptosis occurs invitro and invivo. Furthermore, PAL can prevent carcinogenesis and improve the survival rate of oral cancer, especially tongue cancer, by changing collagenous matrix formation via LOX suppression.