Promotion of Ferroptosis in Oral Cancer Cell Lines by Chrysophanol

Oral cancer is a type of head and neck cancer that can be life threatening if not diagnosed and treated early. Ferroptosis is a type of programmed or regulated cell death dependent on iron and reactive oxygen species but is a caspase-independent form of non-apoptotic cell death. Therefore, there is a need to identify candidate natural compound that may attenuate carcinogenesis through ferroptosis. To this end, we determined the pharmacological effects of chrysophanol on ferroptosis in two different oral cancer cell lines—FaDu, a hypopharyngeal squamous cell carcinoma and SAS, a poorly differentiated squamous cell carcinoma cell line from human tongue primary lesion. Results indicated that chrysophanol caused overproduction of lipid reactive oxygen species, decreased the level of glutathione peroxidase 4, and increased the level of lipocalin-2 and CCAAT-enhancer-binding protein homologous protein. These findings suggest that chrysophanol has the therapeutic potential to alleviate the progression of oral carcinogenesis through activation of ferroptosis.