Expression proteomics study to determine metallodrug targets and optimal drug combinations

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 an...

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Autores principales:	Ronald F. S. Lee, Alexey Chernobrovkin, Dorothea Rutishauser, Claire S. Allardyce, David Hacker, Kai Johnsson, Roman A. Zubarev, Paul J. Dyson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4de57fb3c86d42eab3c5f8158d0517a9
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spelling	oai:doaj.org-article:4de57fb3c86d42eab3c5f8158d0517a92021-12-02T11:53:06ZExpression proteomics study to determine metallodrug targets and optimal drug combinations10.1038/s41598-017-01643-12045-2322https://doaj.org/article/4de57fb3c86d42eab3c5f8158d0517a92017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01643-1https://doaj.org/toc/2045-2322Abstract 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.Ronald F. S. LeeAlexey ChernobrovkinDorothea RutishauserClaire S. AllardyceDavid HackerKai JohnssonRoman A. ZubarevPaul J. DysonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ronald F. S. Lee Alexey Chernobrovkin Dorothea Rutishauser Claire S. Allardyce David Hacker Kai Johnsson Roman A. Zubarev Paul J. Dyson Expression proteomics study to determine metallodrug targets and optimal drug combinations
description	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.
format	article
author	Ronald F. S. Lee Alexey Chernobrovkin Dorothea Rutishauser Claire S. Allardyce David Hacker Kai Johnsson Roman A. Zubarev Paul J. Dyson
author_facet	Ronald F. S. Lee Alexey Chernobrovkin Dorothea Rutishauser Claire S. Allardyce David Hacker Kai Johnsson Roman A. Zubarev Paul J. Dyson
author_sort	Ronald F. S. Lee
title	Expression proteomics study to determine metallodrug targets and optimal drug combinations
title_short	Expression proteomics study to determine metallodrug targets and optimal drug combinations
title_full	Expression proteomics study to determine metallodrug targets and optimal drug combinations
title_fullStr	Expression proteomics study to determine metallodrug targets and optimal drug combinations
title_full_unstemmed	Expression proteomics study to determine metallodrug targets and optimal drug combinations
title_sort	expression proteomics study to determine metallodrug targets and optimal drug combinations
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4de57fb3c86d42eab3c5f8158d0517a9
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Expression proteomics study to determine metallodrug targets and optimal drug combinations

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