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Cisplatin, oxaliplatin, and carboplatin unequally inhibit in vitro mRNA translation

Jonas Philipp Becker1, Johanna Weiss1, Dirk Theile1

  • 1Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Toxicology Letters
|November 27, 2013
PubMed

Insights

Platinum drugs like cisplatin can impact protein synthesis by affecting messenger RNA (mRNA). This study shows cisplatin, but not oxaliplatin or carboplatin, significantly inhibits mRNA translation, revealing mRNA as a functional target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Platinum-based chemotherapy agents, including cisplatin, oxaliplatin, and carboplatin, are known to target DNA.
  • Limited research exists on the interaction of these platinum drugs with messenger RNA (mRNA) and their differential effects on protein synthesis inhibition.

Purpose of the Study:

  • To investigate the effects of cisplatin, oxaliplatin, and carboplatin on mRNA translation in vitro.
  • To determine if mRNA is a functional target for platinum-based antineoplastic agents.

Main Methods:

  • An in vitro translation system was established using mRNA encoding green fluorescent protein (GFP).
  • GFP mRNA was exposed to varying concentrations (0-100 μM) of cisplatin, oxaliplatin, or carboplatin.
  • Drug-mRNA interactions were assessed by monitoring crossing-points in quantitative real-time polymerase chain reactions (qRT-PCR).
  • The impact on protein synthesis was evaluated by measuring GFP translation.

Main Results:

  • Cisplatin (100 μM) significantly increased qRT-PCR crossing-points and markedly reduced GFP mRNA translation.
  • Oxaliplatin exhibited a trend towards reduced GFP mRNA translation.
  • Carboplatin did not significantly affect GFP mRNA translation.

Conclusions:

  • This study provides the first evidence of differential effects of platinum cytostatics on mRNA translation.
  • Messenger RNA (mRNA) is demonstrated to be a functionally relevant target for at least cisplatin.
  • The findings suggest distinct mechanisms of action for platinum-based drugs beyond DNA interaction.
Keywords:
CarboplatinCisplatinDDTCGFPIRESIn vitro translationOxaliplatindiethyldithiocarbamategreen fluorescent proteininternal ribosome entry sitemRNA

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