Trehalose Exerts Selective Cytotoxicity Against Tongue Squamous Cell Carcinoma Cells While Exhibiting Limited Cytotoxicity Toward Normal Oral Squamous Cells.

Background: Chemotherapy-induced oral mucositis is a major complication in tongue squamous cell carcinoma (TSCC) treatment, caused by non-selective cytotoxicity of chemotherapeutic agents. Trehalose is a natural disaccharide with reported antitumor and cell-preserving properties, but its selective effect on TSCC versus normal oral cells remains unclear. This study aimed to evaluate whether trehalose exerts differential effects on TSCC cells and normal oral squamous cells (NOSCs). Methods: We treated two TSCC cell lines (CAL-27, SCC-15) and normal oral squamous cells (NOSCs) with trehalose at different concentrations. Cell proliferation, apoptosis, migration and invasion were evaluated in vitro. Angiogenesis was assessed using the chick embryo chorioallantoic membrane assay, and in vivo antitumor activity was verified in a nude mouse xenograft model. Results: At 200 mmol/L, trehalose significantly inhibited proliferation, migration and invasion, and induced apoptosis in TSCC cells, while showing comparatively limited cytotoxicity toward NOSCs. Trehalose also reduced angiogenic activity in the CAM assay and decreased tumor growth and was associated with less extensive Ki-67 immunostaining in vivo. IL-1β, IL-6, and TNF-α levels increased after trehalose treatment; these changes were considered treatment-associated responses rather than evidence of a causal mechanism of apoptosis. Conclusion: Trehalose selectively inhibited TSCC cells while showing comparatively limited cytotoxicity toward normal oral cells. These findings support further investigation of trehalose as a potential antitumor candidate, while its possible relevance to chemotherapy-induced oral mucositis requires direct validation in dedicated models.