Therapeutic Potential of Allomyrinasin in Oral Squamous Cell Carcinoma via Decreased NBC Activity

Background/Objectives: Allomyrinasin is a cationic antimicrobial peptide derived from Allomyrina dichotoma larvae with known antibacterial and anti-inflammatory properties; however, its effects on migration-related mechanisms in oral squamous cell carcinoma (OSCC) remain poorly understood. This study investigated the anti-migratory potential of allomyrinasin in OSCC cells, focusing on Na⁺/HCO₃^- cotransporter (NBC) activity as a key migratory module. Methods: NBC activity was assessed in YD-38 OSCC cells treated with allomyrinasin. Cell migration was evaluated by wound healing and Transwell assays, and MMP expression. Intracellular reactive oxygen species (ROS), apoptosis-related markers, and lamin A/C expression were analyzed using fluorescence-based assays and gene expression analysis. Results: Allomyrinasin inhibited NBC activity and suppressed cell migration without substantial loss of cell viability. MMP-13 was selectively downregulated among the tested MMPs. Lamin A/C expression was markedly upregulated, suggesting enhanced nuclear stiffness that may restrict confined cell migration. Intracellular ROS levels were elevated, and apoptotic progression was confirmed by increased Annexin V/PI positivity along with downregulation of B-cell lymphoma 2 (BCL2) and upregulation of BCL-2-associated X genes (BAX), through a p53-independent pathway consistent with the TP53-deleted status of YD-38 cells. Conclusions: Allomyrinasin suppresses OSCC cell migration by targeting NBC activity as a key component of the migratory machinery, accompanied by oxidative stress induction and pro-apoptotic signaling. These findings identify allomyrinasin as a potential anti-migratory therapeutic candidate and highlight NBC activity as a promising target for attenuating cancer metastasis.