Anti-tumor activities of the host-defense peptide hymenochirin-1B

Samir Attoub, Hama Arafat, Milena Mechkarska, J. Michael Conlon

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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±0.2μM), breast adenocarcinoma MDA-MB-231 cells (LC50=9.0±0.3μM), colorectal adenocarcinoma HT-29 cells (LC50=9.7±0.2μM), and hepatocarcinoma HepG2 cells (LC50=22.5±1.4μM) with appreciably less hemolytic activity against human erythrocytes (LC50=213±18μM). Structure-activity relationships were investigated by synthesizing analogs of hymenochirin-1B in which Pro5, Glu6 and Asp9on 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 6fold) but hemolytic activity also increases (LC50=174±12μM). The [D9k] and [E6k,D9k] analogs retain relatively high cytotoxic potency against the tumor cells (LC50 in the range 2.1-21μM) but show reduced hemolytic activity (LC50>300μM). The data suggest that hymenochirin-1B has therapeutic potential as a template to generate potent, non-toxic anti-cancer agents.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalRegulatory Peptides
Volume187
DOIs
Publication statusPublished - Nov 10 2013

Keywords

  • Anti-cancer
  • Frog skin
  • Host-defense peptide
  • Hymenochirin
  • Structure-activity

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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