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

Expression proteomics study to determine metallodrug targets and optimal drug combinations

Ronald F S Lee  1 , Alexey Chernobrovkin  2 , Dorothea Rutishauser  2   3 , Claire S Allardyce  1 , David Hacker  4 , Kai Johnsson  1 , Roman A Zubarev  2 , Paul J Dyson  5
Affiliations

Expression proteomics study to determine metallodrug targets and optimal drug combinations

Ronald F S Lee et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Anti-cancer compounds mentioned in this study.
Figure 2
Figure 2
Schematic of the approach used in this study. For more details concerning the FITExP method refer to ref. .
See this image and copyright information in PMC

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