Investigations into the potential anticancer activity of Maximin H5

Dennison, Sarah Rachel orcid iconORCID: 0000-0003-4863-9607, Harris, Frederick and Phoenix, David A. (2017) Investigations into the potential anticancer activity of Maximin H5. Biochimie, 137 . pp. 29-34. ISSN 0300-9084

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Official URL: http://dx.doi.org/10.1016/j.biochi.2017.02.013

Abstract

Here we report the first major example of anionic amphibian host defence peptides (HDPs) with anticancer activity. Maximin H5 is a C-terminally amidated, anionic host defence peptide (MH5N) from toads of the Bombina genus, which was shown to possess activity against the glioma cell line, T98G (EC50 = 125 μM). The peptide adopted high levels of α-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 (Π = 10.5 mN m-1), which correlated with levels of DMPS (R2 > 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 α-helical structure in the presence of cancer membrane mimics (44.8%) along with a reduced ability to penetrate these membranes (Π = 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.


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