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Biochimie. 2017 Jun;137:29-34. doi: 10.1016/j.biochi.2017.02.013. Epub 2017 Feb 27.

Investigations into the potential anticancer activity of Maximin H5.

Author information

1
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
2
School of Forensic and Investigative Science, University of Central Lancashire, Preston PR1 2HE, UK.
3
School of Applied Science, London South Bank University, 103 Borough Road, London SE1 0AA, UK. Electronic address: phoenixd@lsbu.ac.uk.

Abstract

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 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.

KEYWORDS:

Anticancer activity; Host defence peptides; Lipid monolayers; Maximin H5; Membranolytic; α-Helical peptide

PMID:
28249727
DOI:
10.1016/j.biochi.2017.02.013
[Indexed for MEDLINE]

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