Sodium Cantharidate Induces Apoptosis in Tongue Squamous Cell Carcinoma via p53 Targeting: Validation in Xenografts and Organoids

INTRODUCTION: Tongue Squamous Cell Carcinoma (TSCC) is a prevalent head and neck malignancy with limited targeted therapies and minimal toxicity. Sodium Cantharidate (SCA), a natural compound, exhibits anti-tumor potential, but its molecular targets in TSCC remain undefined. This study aimed to evaluate SCA's anti-TSCC efficacy in preclinical models and elucidate its mechanism of action. METHODS: SCA's effects on TSCC cells were assessed using CCK-8 viability, scratch wound healing, Transwell migration/invasion, and flow cytometry (apoptosis). Efficacy was further evaluated in nude mouse xenograft models and patient-derived TSCC organoids. Molecular mechanisms were investigated via Western blotting. RESULTS: SCA significantly inhibited TSCC cell proliferation, migration, and invasion, and induced dose-dependent apoptosis in vitro. It demonstrated cytotoxicity in xenografts and organoids. Western blotting showed SCA upregulated p53 protein and phosphorylation at Ser33, Ser37, and Ser46. Pro-apoptotic BAX and cleaved Caspase 3 increased, while anti-apoptotic BCL-2 decreased, significantly lowering the BCL-2/BAX ratio. DISCUSSION: SCA attenuates TSCC growth and invasion in vitro and in vivo, primarily by inducing apoptosis through modulation of p53 phosphorylation. This is the first study to validate SCA's efficacy using patient-derived TSCC organoids, highlighting their value for pre-clinical drug assessment. While promising, further mechanistic depth is warranted. The results support SCA's potential for clinical translation. CONCLUSION: SCA potently inhibits TSCC progression in cell lines, xenografts, and patient-derived organoids. Its mechanism involves activation of p53 phosphorylation, shifting the BCL-2/BAX balance, and triggering caspase-dependent apoptosis. These findings position SCA as a promising therapeutic candidate and underscore the utility of organoid models in oncology drug development.