Enhanced Inhibition of HNSCC Growth by α-Tomatine and Cisplatin via MAPK-Mediated Apoptosis

Head and neck squamous cell carcinoma (HNSCC) is frequently associated with cisplatin resistance, which limits the therapeutic efficacy of conventional chemotherapy. In this study, we investigated whether α-tomatine could enhance cisplatin sensitivity and augment its antitumor efficacy in HNSCC cells. Treatment with 20 μM cisplatin alone induced relatively low cytotoxicity in FaDu and YD38 cells (18.45 ± 2.59% and 9.40 ± 2.33%, respectively). In contrast, co-treatment of FaDu and YD38 cells with cisplatin (20 μM) and a non-cytotoxic concentration of α-tomatine (2 μM) significantly increased cell death to 52.98 ± 7.84% and 40.40 ± 3.06%, respectively, compared with cisplatin monotherapy. The combination treatment markedly suppressed colony formation, indicating reduced clonogenic survival, and significantly enhanced apoptosis through the simultaneous activation of intrinsic and extrinsic apoptotic pathways. The enhanced apoptosis was driven by the activation of the mitogen-activated protein kinase (MAPK) signaling cascade. Furthermore, the enhanced antitumor effect of α-tomatine and cisplatin was confirmed in a xenograft tumor model. These findings demonstrate that α-tomatine enhances cisplatin-induced apoptosis via MAPK-mediated signaling, supporting its role as a chemosensitizing agent for HNSCC.