Antitumour and apoptotic effects of a novel Tris-peptide complex obtained after isolation of Raoultella ornithinolytica extracellular metabolites

J Appl Microbiol. 2015 Jun;118(6):1357-69. doi: 10.1111/jam.12806. Epub 2015 Apr 22.

Abstract

Aims: The characterization of the antitumour activity and chemical identification of the compounds obtained after the isolation of extracellular metabolites of bacteria Raoultella ornithinolytica.

Methods and results: The fraction with anticancer activity against the HeLa cell line, T47D and TOV-112D was obtained from the supernatants of R. ornithinolytica culture using ion-exchange chromatography, and separated by Sephadex G-50 medium gel filtration into two subfractions. The obtained compounds were analysed using Fourier Transform-Infrared Spectroscopy, Raman spectroscopy and matrix-assisted laser desorption/ionization MS/MS spectrometry. The antitumour activity of the two subfractions was analysed using 5-bromo-2-deoxy-uridine kit. The subfraction with the highest activity against HeLa cells was identified as Tris-peptide complex. The amino acid sequence of the peptide from the complex was found to be TDAPSFSDIPN and molecular weight was estimated at 1430·6576 Da. Cytotoxic, cytopathic and apoptotic effects in HeLa cells treated with the active complex were observed; however, the cytotoxic effect against normal human skin fibroblasts was minimal.

Conclusions: The Tris-peptide complex from R. ornithinolytica showed selective antitumour activity against the HeLa cell line.

Significance and impact of the study: The Tris-peptide complex due to the high selectivity can be used in biomedicine, and its derivatives may contribute to the development of new anticancer compounds.

Keywords: anticancer; bioproduct; casein-derived peptide; earthworm; gut bacterium.

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Chromatography, Gel
  • Enterobacteriaceae / chemistry*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Molecular Weight
  • Peptides / chemistry
  • Peptides / isolation & purification
  • Peptides / pharmacology*
  • Spectroscopy, Fourier Transform Infrared
  • Tandem Mass Spectrometry

Substances

  • Antineoplastic Agents
  • Peptides

Associated data

  • GENBANK/FJ905041