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 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.

Keywords::

• Host defense peptide
• plasma cell myeloma
• cytolysis
• DNA fragmentation

Acknowledgements

This work was supported by a Capital Health Research Grant. A.H. and C.D. were supported by Postgraduate Scholarships from NSERC. D.C. was supported by a Dalhousie University Faculty of Medicine Summer Fellowship. T.Z. is supported by a trainee award from The Beatrice Hunter Cancer Research Institute with funds provided by Cancer Care Nova Scotia as part of the Terry Fox Strategic Health Research Training Program in Cancer Research at CIHR. We thank Susan Douglas and Aleksander Patrzykat (Institute for Marine Biosciences, National Research Council) for helpful discussions, and Tony Reiman (Saint John Regional Hospital) for providing the human multiple myeloma cell lines. We also acknowledge the support of the Canada Foundation for Innovation, the Atlantic Innovation Fund, NSERC, and other partners that fund the Facilities for Materials Characterization, managed by the Institute for Research in Materials.

Potential conflict of interest:

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