Mastoparan is a membranolytic anti-cancer peptide that works synergistically with gemcitabine in a mouse model of mammary carcinoma

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3195-3204
Number of pages10
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1858
Issue number12
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • Anti-cancer peptide
  • Breast cancer
  • Broad-spectrum
  • Leukemia
  • Membrane lysis
  • Synergy

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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