Anticancer Activity of the Goat Antimicrobial Peptide ChMAP-28

Author:

Emelianova, Anna A.  Kuzmin, Denis V.  Panteleev, Pavel V.  Sorokin, Maxim  Buzdin, Anton A.  Ovchinnikova, Tatiana V.  

Journal:

FRONTIERS IN PHARMACOLOGY

Issue Date:

2018

Abstract(summary):

Cytotoxic effect of the antimicrobial peptide ChMAP-28 from leucocytes of the goat Capra hircus was examined against five cancer and two normal human cell lines. ChMAP-28 has the amino acid sequence GRFKRFRKKLKRLWHKVGPFVGPILHY and is homologous to other alpha-helical mammalian antimicrobial peptides. ChMAP-28 shows considerably higher cytotoxicity against cultured tumor cells than toward normal cells at concentrations of < 10 mu M. Our findings suggest that ChMAP-28 can initiate necrotic death of cancer cells. Its cytotoxic effect is accomplished due to disruption of the plasma membrane integrity and is not abrogated by the addition of the caspase inhibitor Z-VAD-FMK. ChMAP-28 causes permeabilization of cytoplasmic membrane of human leukemia cells HL-60 already after 15 min of incubation. Here, we show that ChMAP-28 has one of the highest antitumor activity in vitro among all known antimicrobial peptides. We speculate that the observed specificity of ChMAP-28 cytotoxic effect against tumor cells is due to its relatively low hydrophobicity and high cationicity. In the meantime, this peptide has low hemolytic activity, which generates a potential for its use as a therapeutic agent.