title: Investigations into the potential anticancer activity of Maximin H5.
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.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Dennison
authors.affiliation: School of Forensic and Investigative Science, University of Central Lancashire, Preston PR1 2HE, UK.
authors.forename: Frederick
authors.initials: F
authors.lastname: Harris
authors.affiliation: School of Applied Science, London South Bank University, 103 Borough Road, London SE1 0AA, UK. Electronic address: phoenixd@lsbu.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Phoenix
mesh_terms: D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001001:Anura / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D029845:Amphibian Proteins; D000970:Antineoplastic Agents; D008055:Lipids; D010446:Peptide Fragments; C464648:maximin H5, Bombina maxima
keywords: Anticancer activity; Host defence peptides; Lipid monolayers; Maximin H5; Membranolytic; α-Helical peptide