Lactoferrin-Derived Peptide Chimera Induces Caspase-independent Cell Death in Multiple Myeloma

Abstract

Lactoferrin-derived peptide chimera is a synthetic peptide that mimics the functional unit of lactoferrin with antibacterial activity. Antimicrobial peptides are promising candidates for cancer treatment. Although LF is known to have anticancer effects, to the best of our knowledge, its effects on multiple myeloma have not yet been studied. In this study, we explored the potential of lactoferrin-derived chimera for the treatment of multiple myeloma, a malignant clonal plasma cell disease of the bone marrow. Lactoferrin-derived chimera effectively inhibited MM1S, MM1R, and RPMI8226 multiple myeloma cell growth and induced the early and late phases of apoptosis, but not in normal peripheral blood mononuclear cells. Furthermore, lactoferrin-derived chimera modulates the relative expression of genes involved in survival, apoptosis, and mitochondrial dysfunction at the transcriptional level. Mitochondrial analysis revealed that lactoferrin-derived chimera triggered oxidative stress in multiple myeloma cells, leading to the generation of reactive oxygen species and a decline in mitochondrial membrane potential, resulting in mitochondrial dysfunction. Although lactoferrin-derived chimera did not cause caspase-dependent cell death, it induced nuclear translocation of apoptosis-inducing factor and endonuclease G, indicating the initiation of caspase-independent apoptosis. Overall, our data suggest that lactoferrin-derived chimera induces caspase-independent programmed cell death in multiple myeloma cell lines by increasing the nuclear translocation of apoptosis-inducing factor/endonuclease G. Therefore, lactoferrin-derived chimera has potential in multiple myeloma cancer therapies.