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The Acute Phase Protein Hepcidin Is Cytotoxic to Human and Mouse Myeloma Cells
David M Conrad1,2,3, Ashley L Hilchie4, Katelyn A M McMillan4
1Department of Pathology & Laboratory Medicine, Division of Hematopathology, Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
Background/Aim:
Hepcidin is a cationic acute phase reactant synthesized by the liver. It has bactericidal properties and is a major regulator of iron homeostasis. Cationic antimicrobial peptides represent an innate antimicrobial defense system. We hypothesized that, like other cationic antimicrobial peptides, hepcidin is cytotoxic to cancer cells.
Materials And Methods:
The cytotoxicity of human hepcidin against myeloma cells was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and DNA fragmentation assays. Plasma membrane damage was quantified by propidium iodide (PI) staining. Cell membrane changes were visualized by scanning electron microscopy.
Results:
Hepcidin impaired myeloma cell survival and induced DNA fragmentation. PI staining and scanning electron microscopy revealed hepcidin-induced disruption of the plasma membrane.
Conclusion:
Human hepcidin is an anti-cancer peptide that induces myeloma cell lysis, and therefore may play a role in innate anticancer immunity. To our knowledge, this is the first biological function ascribed to human hepcidin that is not related to its antimicrobial and iron-regulatory properties.
Insights
Human hepcidin, an iron-regulating peptide, demonstrates anti-cancer properties. It effectively reduces myeloma cell survival and induces cancer cell lysis, suggesting a role in innate anticancer immunity.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Hepcidin is a liver-synthesized peptide with antimicrobial and iron-regulating functions.
- Cationic antimicrobial peptides are part of the innate immune system.
- Hepcidin's potential cytotoxic effects on cancer cells were unexplored.
Purpose of the Study:
- To investigate the anti-cancer activity of human hepcidin.
- To determine if hepcidin exhibits cytotoxicity against myeloma cells.
Main Methods:
- Assessed hepcidin cytotoxicity using MTT and DNA fragmentation assays.
- Quantified plasma membrane damage via propidium iodide (PI) staining.
- Visualized cell membrane alterations using scanning electron microscopy.
Main Results:
- Hepcidin significantly impaired myeloma cell survival.
- Induced DNA fragmentation in myeloma cells.
- Demonstrated hepcidin-induced disruption of the plasma membrane.
Conclusions:
- Human hepcidin acts as an anti-cancer peptide.
- Hepcidin induces myeloma cell lysis, indicating a role in innate anticancer immunity.
- This study reveals a novel, non-antimicrobial, non-iron-regulatory function for hepcidin.
