Expression proteomics study to determine metallodrug targets and optimal drug combinations

Sci Rep. 2017 May 8;7(1):1590. doi: 10.1038/s41598-017-01643-1.

Abstract

The emerging technique termed functional identification of target by expression proteomics (FITExP) has been shown to identify the key protein targets of anti-cancer drugs. Here, we use this approach to elucidate the proteins involved in the mechanism of action of two ruthenium(II)-based anti-cancer compounds, RAPTA-T and RAPTA-EA in breast cancer cells, revealing significant differences in the proteins upregulated. RAPTA-T causes upregulation of multiple proteins suggesting a broad mechanism of action involving suppression of both metastasis and tumorigenicity. RAPTA-EA bearing a GST inhibiting ethacrynic acid moiety, causes upregulation of mainly oxidative stress related proteins. The approach used in this work could be applied to the prediction of effective drug combinations to test in cancer chemotherapy clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Chromatography, Liquid
  • Drug Combinations
  • Drug Discovery* / methods
  • Drug Interactions*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Theoretical
  • Molecular Structure
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Proteome / drug effects*
  • Proteomics* / methods
  • Ruthenium / chemistry
  • Tandem Mass Spectrometry

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • Organometallic Compounds
  • Proteome
  • Ruthenium