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

Ashley L. Hilchie; David M. Conrad; Melanie R. Power Coombs; Tyler Zemlak; Carolyn D. Doucette; Robert S. Liwski; David W. Hoskin

doi:10.3109/10428194.2013.770847

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

Ashley L. Hilchie, David M. Conrad, Melanie R. Power Coombs, Tyler Zemlak, Carolyn D. Doucette, Robert S. Liwski, David W. Hoskin

Medicine

Medicine

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2255-2262
Number of pages	8
Journal	Leukemia and Lymphoma
Volume	54
Issue number	10
DOIs	https://doi.org/10.3109/10428194.2013.770847
Publication status	Published - Oct 2013

Bibliographical note

Funding Information:
Th is 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.

ASJC Scopus Subject Areas

Hematology
Oncology
Cancer Research

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3109/10428194.2013.770847

Cite this

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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.",

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

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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