Sennoside A Modulates the Ferroptosis and Immune Evasion of Oral Squamous Cell Carcinoma Cells Through Inhibiting the NF-κB Pathway.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is an invasive cancer with a high rate of metastasis and recurrence. Anthraquinone natural active element sennoside A (SA) has demonstrated a repressive effect on several malignancies. Its impact on OSCC is still unknown, though. METHODS: The toxicity effect of SA on OSCC cells was examined by CCK8, to screen the appropriate concentrations for following assays. The effect of SA on proliferation, ferroptosis and immune evasion of OSCC was assessed by CCK-8, DCHF-DA staining, biochemical detection, ELISA, and western blotting. The mechanism of SA on OSCC was determined by western blotting and immunofluorescence. Besides, in vivo effect of SA was investigated on tumor-bearing mice using HE staining, immunohistochemistry, and western blotting. RESULTS: SA reduced SCC7 and CAL27 cell viability, with a IC50 values of 94.38 and 77.41 μM, respectively. SA downregulated the expressions of GPX4 and xCT expression and the SOD level, but elevated the levels of ROS, MDA, and Fe(2+) in SCC7 and CAL27 cells. SA decreased the PD-L1 expression, whereas increased the cytotoxicity of CD8(+) T cells and the concentrations of IFN-γ, IL-2, and TNF-α of SCC7 and CAL27 cells. Mechanically, SA reduced the phosphorylation of NF-κB and IκBα in SCC7 and CAL27 cells. Also, RANKL treatment reversed the outcomes of indicators involved in proliferation, ferroptosis and immune evasion in SCC7 cells. In vivo, SA reduced tumor weight and size, the expression levels of GPX4 and PD-L1 and the phosphorylation of NF-κB and IκBα, but enhanced the IFN-γ level in mice xenografted with SCC7 cells. CONCLUSION: SA suppressed proliferation and immune evasion, but induced ferroptosis through the inactivation of NF-κB pathway in OSCC.