Hepcidin is cytotoxic to myeloma cells (P1337)

Abstract

Abstract Recent studies suggest that some cationic antimicrobial peptides (CAPs) contribute to innate anticancer immunity. Hepcidin is a CAP and acute phase reactant well known for its antibacterial properties and its role in iron homeostasis. No anticancer function has yet been assigned to hepcidin, although elevated hepcidin levels are found in patients with hematologic malignancies, including plasma cell myeloma. We therefore investigated the anticancer properties of hepcidin against myeloma cells in vitro. A hepcidin isoform lacking the iron-regulatory domain was used. Hepcidin toxicity was assessed by MTT survival assays and DNA fragmentation tests. Propidium iodide (PI) staining was used to measure plasma membrane damage, and scanning electron microscopy (SEM) was performed to visualize cellular membrane changes. Hepcidin impaired the survival of mouse and human myeloma cells and induced DNA fragmentation, suggesting that cytotoxicity may be due to apoptosis. Hepcidin caused substantial PI uptake in the myeloma cells, and SEM confirmed that hepcidin treatment resulted in cellular membrane pore formation. Interestingly, hepcidin was more toxic to melphalan-resistant myeloma cells than to melphalan-sensitive controls. Our data implicate a role for hepcidin in innate immunity against plasma cell myeloma. Further studies on the anticancer properties of hepcidin are warranted in order to fully understand its physiological role in the context of neoplastic disease.