TanshinoneIIA exerts protective effects via attenuate FTH1, a biomarker and therapeutic target in head and neck Squamous Cell Carcinoma

Background TanshinoneIIA (TanIIA) refers to one of the major lipophilic bioactive components of S. miltiorrhiza that exerts multiple pleiotropic effects (e.g., anti-inflammatory effects, antioxidant, and anti-tumor effects). Head and neck squamous cell carcinoma (HNSCC) is recognized as the sixth most common cancer worldwide. As indicated from existing studies, ferroptosis may be responsible for its progression. However, the underlying mechanisms have not been overall clarified. This study aimed to screen a functional therapeutic target in HNSCC to specifically analyze its correlation with HNSCC and whether TanIIA can act on it to exert a therapeutic effect. Methods Data originating from GEO series GSE6631 and GSE13398 datasets were analyzed with the limma R package on GEO2R to find differentially expressed genes between healthy people from HNSCC patients. The DEG-related PPI network was built with the STRING database, and then the visualization was conducted by Cytoscape. FTH1 expression and mapping were examined with Human Protein Atlas, and FTH1 protein analysis and Kaplan-Meier analysis were conducted to carry out survival analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) were used to localize FTH1 in HNSCCs. The protein expressions were analyzed with Western-blot method. The cell survival and invasion ability were identified by employing CCK-8 and Transwell methods. Results A high FTH1 expression in the HNSCCs sample could indicate poor patient outcome. TanIIA at certain concentrations could significantly attenuate FTH1 expression and reduce HNSCCs survival and invasion. Conclusions As revealed from this study, FTH1 could act as a promising therapy target in HNSCC and can be inhibited by TanIIA, which was demonstrated to carry out anticancer activities with less side effect.