Here we report the first major example of anionic amphibian host defence peptides (HDPs) with anticancer activity. Maximin H5 (MH5N) is a C-terminally amidated, anionic host defence peptide from toads of the Bombina genus, which was shown to possess activity against the glioma cell line, T98G (EC50 = 125 mu M). The peptide adopted high levels of alpha-helical structure (57.3%) in the presence of model cancer membranes (DMPC:DMPS in a molar ratio of 10:1). MH5N also showed a strong ability to penetrate these model membranes (Pi = 10.5 mN m(-1)), which correlated with levels of DMPS (R-2 > 0.98). Taken with the high ability of the peptide to lyse these membranes (65.7%), it is proposed that maximin H5 kills cancer cells via membranolytic mechanisms that are promoted by anionic lipid. It was also found that C-terminally deaminated maximin H5 (MH5C) exhibited lower levels of alpha-helical structure in the presence of cancer membrane mimics (44.8%) along with a reduced ability to penetrate these membranes (Pi = 8.1 mN m(-1)) and induce their lysis (56.6%). These data suggested that the two terminal amide groups of native maximin H5 are required for its optimal membranolytic and anticancer activity. (C) 2017 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
