Mastoparan is a membranolytic anti-cancer peptide that works synergistically with gemcitabine in a mouse model of mammary carcinoma.
Anti-cancer peptides (ACPs) are small cationic and hydrophobic peptides that are more toxic to cancer cells than normal cells. ACPs kill cancer cells by causing irreparable membrane damage and cell lysis, or by inducing apoptosis. Direct-acting ACPs do not bind to a unique receptor, but are rather attracted to several different molecules on the surface of cancer cells. Here we report that an amidated wasp venom peptide, Mastoparan, exhibited potent anti-cancer activities toward leukemia (IC50~8-9.2μM), myeloma (IC50~11μM), and breast cancer cells (IC50~20-24μM), including multidrug resistant and slow growing cancer cells. Importantly, the potency and mechanism of cancer cell killing was related to the amidation of the C-terminal carboxyl group. Mastoparan was less toxic to normal cells than it was to cancer cells (e.g., IC50to PBMC=48μM). Mastoparan killed cancer cells by a lytic mechanism. Moreover, Mastoparan enhanced etoposide-induced cell death in vitro. Our data also suggest that Mastoparan and gemcitabine work synergistically in a mouse model of mammary carcinoma. Collectively, these data demonstrate that Mastoparan is a broad-spectrum, direct-acting ACP that warrants additional study as a new therapeutic agent for the treatment of various cancers.
University of British Columbia, Vancouver, BC, Canada.
Ashley L
AL
Hilchie
University of British Columbia, Vancouver, BC, Canada.
Andrew J
AJ
Sharon
University of British Columbia, Vancouver, BC, Canada.
Evan F
EF
Haney
Dalhousie University, Halifax, NS, Canada.
David W
DW
Hoskin
BC Cancer Agency, Vancouver, BC, Canada.
Marcel B
MB
Bally
Departamento de Patologia Molecular, Universidade de Brasília, DF, Brazil; Centro de Análises Proteômicas e Bioquímicas, Universidade, Católica de Brasília, DF, Brazil; S-Inova Biotech, Programa de Pós Graduação em Biotecnologia, Universidade Católica Dom Bosco, Campo Grande, MS, Brazil.
Octavio L
OL
Franco
Dalhousie University, Halifax, NS, Canada.
Jennifer A
JA
Corcoran
University of British Columbia, Vancouver, BC, Canada. Electronic address: bob@hancocklab.com.
Robert E W
REW
Hancock
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects*; D002942:Circular Dichroism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D014862:Wasp Venoms / Q000494:pharmacology*; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D003841:Deoxycytidine; C037500:mastoparan; D000093542:Gemcitabine
Anti-cancer peptide; Breast cancer; Broad-spectrum; Leukemia; Membrane lysis; Synergy
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