Title
Mastoparan is a membranolytic anti-cancer peptide that works synergistically with gemcitabine in a mouse model of mammary carcinoma
Author
Ashley L. Hilchie, Andrew J. Sharon, Evan F. Haney, David W. Hoskin, Marcel B. Bally, Octavio L. Franco, Jennifer A. Corcoran, Robert E.W. Hancock
Year
2016
Journal
Biochimica et Biophysica Acta (BBA) - Biomembranes
Abstract
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 ~ 8–9.2 μM), myeloma (IC50 ~ 11 μM), and breast cancer cells (IC50 ~ 20–24 μM), 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., IC50 to PBMC = 48 μM). 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.
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Vesicle interactions, Chemical stability, Biochemistry