title: Anti-tumor activities of the host-defense peptide hymenochirin-1B.
abstract: The hymenochirins are a family of cationic, amphipathic, α-helical host-defense peptides, first isolated from skin secretions of the Congo clawed frog Hymenochirus boettgeri (Pipidae). Of the four hymenochirins tested, hymenochirin-1B (IKLSPETKDNLKKVLKGAIKGAIVAKMV.NH2) shows the greatest cytotoxic potency against non-small cell lung adenocarcinoma A549 cells (LC50=2.5±0.2 μM), breast adenocarcinoma MDA-MB-231 cells (LC50=9.0±0.3 μM), colorectal adenocarcinoma HT-29 cells (LC50=9.7±0.2 μM), and hepatocarcinoma HepG2 cells (LC50=22.5±1.4 μM) with appreciably less hemolytic activity against human erythrocytes (LC50=213±18μM). Structure-activity relationships were investigated by synthesizing analogs of hymenochirin-1B in which Pro(5), Glu(6) and Asp(9)on the hydrophilic face of the helix were replaced by one or more L-lysine or D-lysine residues. The [D9K] analog displays the greatest increase in potency against all four cell lines (up to 6 fold) but hemolytic activity also increases (LC50=174±12 μM). The [D9k] and [E6k,D9k] analogs retain relatively high cytotoxic potency against the tumor cells (LC50 in the range 2.1-21 μM) but show reduced hemolytic activity (LC50>300 μM). The data suggest that hymenochirin-1B has therapeutic potential as a template to generate potent, non-toxic anti-cancer agents.
authors.affiliation: Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.forename: Hama
authors.initials: H
authors.lastname: Arafat
authors.forename: Milena
authors.initials: M
authors.lastname: Mechkarska
authors.forename: J Michael
authors.initials: JM
authors.lastname: Conlon
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; C000589575:hymenochirin-1B, Hymenochirus boettgeri
keywords: Anti-cancer; Frog skin; Host-defense peptide; Hymenochirin; Structure–activity