Antitumor effect of the antimicrobial peptide GLI13-8 derived from domain of the avian β-defensin-4

Acta Biochim Biophys Sin (Shanghai). 2013 Nov;45(11):904-11. doi: 10.1093/abbs/gmt098. Epub 2013 Sep 18.

Abstract

We previously reported that GLI13-8, one of cationic antimicrobial peptides from linear avian β-defensin-4 (RL38) analogs, exhibited high antimicrobial activities against both Gram-negative and Gram-positive bacteria. In the present study, we reported the in vitro cytotoxicity of GLI13-8 using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results showed that the cytotoxicity of GLI13-8 in three human carcinoma cells (HepG2, SGC7901, and A375) was in a dose-dependent manner. When the concentration of GLI13-8 is <128 μM, it had no toxicity towards the normal human fibroblasts (MRC-5). The Annexin-V-FITC/PI staining assay, the Hoechst 33258/PI staining assay, the permeability of fluorescein macromolecules and scanning electron microscope assays, mitochondrial membrane potential assay, caspases-3 and poly ADP-ribose polymerase (PARP) assays have been carried out. Results indicated that apoptosis was induced by GLI13-8 in HepG2 cells, and demonstrated that GLI13-8 induced loss of mitochondrial membrane potential, disruption of HepG2 cell membranes, and activation of caspase-3 and PARP. These findings suggested that GLI13-8 may be an effective agent for HepG2 cells.

Keywords: AvBD-4 derivative; antimicrobial peptide; apoptosis; carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Birds
  • Caspase 3 / metabolism
  • Cell Membrane Permeability
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fluorescein / pharmacokinetics
  • Hep G2 Cells
  • Humans
  • Membrane Potential, Mitochondrial
  • Microscopy, Electron, Scanning
  • Poly(ADP-ribose) Polymerases / metabolism
  • beta-Defensins / chemistry*

Substances

  • Antimicrobial Cationic Peptides
  • Antineoplastic Agents
  • GLI13-8 peptide
  • beta-Defensins
  • Poly(ADP-ribose) Polymerases
  • Caspase 3
  • Fluorescein