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Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome

Irina V Prokhorova1, Kseniya A Akulich2,3, Desislava S Makeeva2,3

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Université de Strasbourg, 67404, Illkirch, France.

Scientific Reports
|June 15, 2016
PubMed

Insights

Amicoumacin A antibiotic inhibits translation by targeting bacterial ribosomes, affecting elongation in yeast and mammalian systems. Cancer cells show higher susceptibility, suggesting potential for new drug development.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Antimicrobial Research

Background:

  • Amicoumacin A is an antibiotic targeting bacterial ribosomes.
  • It influences translocation and creates an additional binding interface between ribosomal RNA and messenger RNA.
  • The drug's binding site involves universally conserved ribosomal RNA nucleotides.

Purpose of the Study:

  • To investigate amicoumacin A's inhibitory effects on translation in yeast and mammalian systems.
  • To determine the structural basis of amicoumacin A binding to ribosomes.
  • To assess the differential toxicity of amicoumacin A towards cancerous versus non-cancerous cells.

Main Methods:

  • Inhibition assays in yeast and mammalian translation systems.
  • Cryo-electron microscopy to determine the structure of the amicoumacin A-yeast ribosome complex.
  • Toxicity measurements using human cancer and non-cancerous cell lines.

Main Results:

  • Amicoumacin A was shown to inhibit translation elongation in both yeast and mammalian systems.
  • The structure of amicoumacin A complexed with yeast ribosomes was determined at 3.1 Å resolution.
  • Human cancer cell lines exhibited greater susceptibility to amicoumacin A inhibition compared to non-cancerous cells.

Conclusions:

  • Amicoumacin A effectively inhibits translation elongation in eukaryotic systems.
  • The structural data provides insights into the mechanism of action.
  • The differential toxicity suggests potential for developing targeted cancer therapies.

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