Related Experiment Video
Updated: Jan 17, 2026
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Sennoside A Modulates the Ferroptosis and Immune Evasion of Oral Squamous Cell Carcinoma Cells Through Inhibiting the
Jiaying Huo1, Jianhua Qi2, Qixuan Ren1
1Hebei Medical University, Shijiazhuang, Hebei, China.
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 Fe2+ 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.
Insights
Sennoside A (SA) combats oral squamous cell carcinoma (OSCC) by inhibiting proliferation and immune evasion while inducing ferroptosis. This natural compound shows promise in treating OSCC by targeting the NF-κB pathway.
Area of Science:
- Oncology
- Natural Products Chemistry
- Immunology
Background:
- Oral squamous cell carcinoma (OSCC) presents significant challenges due to high metastasis and recurrence rates.
- Sennoside A (SA), an anthraquinone natural product, has shown anti-cancer effects in various malignancies.
- The specific impact of SA on OSCC remains largely unexplored.
Purpose of the Study:
- To investigate the effects of SA on OSCC cell proliferation, ferroptosis, and immune evasion.
- To elucidate the underlying molecular mechanisms of SA action in OSCC.
- To evaluate the in vivo efficacy of SA in a mouse model of OSCC.
Main Methods:
- Cell viability was assessed using CCK8 assays to determine IC50 values.
- Proliferation, ferroptosis, and immune evasion markers were analyzed via DCHF-DA staining, biochemical assays, ELISA, and western blotting.
- In vivo studies involved tumor-bearing mice treated with SA, with analyses including HE staining, immunohistochemistry, and western blotting.
Main Results:
- SA significantly reduced OSCC cell viability and tumor growth in vivo.
- SA induced ferroptosis by downregulating GPX4 and xCT, and increasing ROS, MDA, and Fe2+ levels.
- SA suppressed immune evasion by decreasing PD-L1 expression and enhancing CD8+ T cell cytotoxicity and pro-inflammatory cytokine production (IFN-γ, IL-2, TNF-α).
- SA acted via the NF-κB pathway, reducing NF-κB and IκBα phosphorylation, an effect reversed by RANKL treatment.
Conclusions:
- SA effectively suppresses OSCC proliferation and immune evasion.
- SA induces ferroptosis in OSCC cells through the inactivation of the NF-κB pathway.
- SA demonstrates therapeutic potential for OSCC treatment, both in vitro and in vivo.
