Bee Venom Peptide Melittin Targets Mitochondrial Vulnerabilities in Melanoma via MT-CO1 Regulation 2266872

Abstract

Abstract Introduction Melanoma cells undergo metabolic reprogramming that suppresses mitochondrial oxidative phosphorylation and enhances glycolytic dependence. Transcriptomic analysis shows strong downregulation of the mitochondrial gene MT-CO1, which encodes cytochrome c oxidase subunit I, in the A375 melanoma cell line. Melittin, a peptide from bee venom, has demonstrated potent lytic and pro-apoptotic effects in multiple cancer models through mitochondrial disruption. This project aims to determine whether melittin treatment alters MT-CO1 expression, induces mitochondrial stress, and reduces melanoma cell viability. Methods A375 melanoma cells will be treated with melittin at graded concentrations and time points. MT-CO1 mRNA and protein levels will be quantified by qPCR and Western blotting. Mitochondrial function will be assessed through ATP production and reactive oxygen species (ROS) assays. Computational modeling will predict melittin—membrane interactions and potential apoptotic pathways activated by mitochondrial stress. Results Preliminary analysis predicts that melittin will increase ROS accumulation, impair mitochondrial function, and partially restore MT-CO1 expression relative to untreated controls. Reduced cell viability is expected in a dose-dependent manner, reflecting enhanced sensitivity to mitochondrial disruption. Conclusion Targeting MT-CO1, a downregulated mitochondrial gene in melanoma, with melittin may exploit metabolic vulnerabilities in tumor cells. Melittin-induced mitochondrial stress could promote apoptosis and limit melanoma cell growth, offering a potential therapeutic avenue that integrates natural cytolytic peptides with metabolic targeting strategies. Funding Source n/a Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)