Pleurocidin-family cationic antimicrobial peptides mediate lysis of multiple myeloma cells and impair the growth of multiple myeloma xenografts

Abstract Multiple myeloma is a common hematological malignancy that urgently requires new approaches to treatment, since the disease is not curable using current chemotherapeutic regimens. The aim of this study was to determine whether human and mouse multiple myeloma cells are killed by the pleuroc...

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Bibliographic Details
Published in:Leukemia & lymphoma 2013-10, Vol.54 (10), p.2255-2262
Main Authors: Hilchie, Ashley L., Conrad, David M., Power Coombs, Melanie R., Zemlak, Tyler, Doucette, Carolyn D., Liwski, Robert S., Hoskin, David W.
Format: Article
Language:English
Subjects:
Animals
Antimicrobial Cationic Peptides - administration & dosage
Antimicrobial Cationic Peptides - pharmacology
Antimicrobial Cationic Peptides - toxicity
Cell Line, Tumor
Cell Survival - drug effects
cytolysis
Disease Models, Animal
DNA fragmentation
DNA Fragmentation - drug effects
Female
Fish Proteins - administration & dosage
Fish Proteins - pharmacology
Fish Proteins - toxicity
Host defense peptide
Humans
Mice
Multiple Myeloma - drug therapy
Multiple Myeloma - pathology
plasma cell myeloma
Tumor Burden - drug effects
Xenograft Model Antitumor Assays
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Summary:Abstract Multiple myeloma is a common hematological malignancy that urgently requires new approaches to treatment, since the disease is not curable using current chemotherapeutic regimens. The aim of this study was to determine whether human and mouse multiple myeloma cells are killed by the pleurocidin-like cationic antimicrobial peptides NRC-03 and NRC-07, previously shown to be active against breast cancer cells. We demonstrate here that NRC-03 and NRC-07 bound to and rapidly killed multiple myeloma cells by causing extensive membrane damage, as well as DNA cleavage. NRC-03 showed greater binding to multiple myeloma cells and a more potent cytotoxic effect than NRC-07. In addition, intratumoral injections of NRC-03 impaired the growth of multiple myeloma xenografts in immune-deficient mice. We conclude that NRC-03 warrants further investigation for its possible use in the treatment of multiple myeloma.
ISSN:1042-8194
1029-2403
DOI:10.3109/10428194.2013.770847