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Updated: Mar 2, 2026
Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Expression proteomics study to determine metallodrug targets and optimal drug combinations
Ronald F S Lee1, Alexey Chernobrovkin2, Dorothea Rutishauser2,3
1Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015, Lausanne, Switzerland.
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.
Insights
Functional Identification of Target by Expression Proteomics (FITExP) revealed distinct protein targets for ruthenium(II)-based anti-cancer drugs RAPTA-T and RAPTA-EA. This approach aids in predicting effective cancer drug combinations for clinical trials.
Area of Science:
- Proteomics
- Cancer Biology
- Drug Discovery
Background:
- Ruthenium(II)-based compounds are investigated for anti-cancer properties.
- Understanding drug mechanisms of action is crucial for effective cancer chemotherapy.
- Functional Identification of Target by Expression Proteomics (FITExP) is an emerging technique for identifying protein targets.
Purpose of the Study:
- To elucidate the protein targets and mechanisms of action for ruthenium(II)-based anti-cancer compounds RAPTA-T and RAPTA-EA in breast cancer cells.
- To compare the proteomic profiles induced by RAPTA-T and RAPTA-EA.
- To assess the potential of FITExP in guiding the selection of anti-cancer drug combinations.
Main Methods:
- Application of the functional identification of target by expression proteomics (FITExP) technique.
- Treatment of breast cancer cells with RAPTA-T and RAPTA-EA.
- Analysis of protein expression profiles to identify upregulated proteins.
Main Results:
- RAPTA-T induced upregulation of multiple proteins, suggesting a broad mechanism of action involving suppression of metastasis and tumorigenicity.
- RAPTA-EA, containing an ethacrynic acid moiety, primarily upregulated oxidative stress-related proteins.
- Significant differences in protein upregulation were observed between RAPTA-T and RAPTA-EA treatments.
Conclusions:
- FITExP effectively identified distinct protein targets for RAPTA-T and RAPTA-EA in breast cancer cells.
- The distinct proteomic responses suggest different mechanisms of action for the two ruthenium compounds.
- The FITExP approach holds promise for predicting effective drug combinations for cancer chemotherapy clinical trials.
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