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1H HR-MAS NMR-Based Metabolomics of Cancer Cells in Response to Treatment with the Diruthenium Trithiolato Complex [(p-MeC6H4iPr)2Ru2(SC6H4-p-But)3]+ (DiRu-1)

1
Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland
2
Department of BioMedical Research and Radiology, University of Bern and Inselspital, Erlachstrasse 9a, 3012 Bern, Switzerland
3
Faculty of Information Technology, Czech Technical University in Prague, Thákurova 9, 16000 Prague, Czech Republic
*
Authors to whom correspondence should be addressed.
Metabolites 2019, 9(7), 146; https://doi.org/10.3390/metabo9070146
Received: 29 May 2019 / Revised: 4 July 2019 / Accepted: 5 July 2019 / Published: 18 July 2019
(This article belongs to the Special Issue NMR-based Metabolomics and Its Applications Volume 2)
The trithiolato bridged diruthenium complex DiRu-1 [(p-MeC6H4iPr)2Ru2(SC6H4-p-But)3]+ is highly cytotoxic against various cancer cell lines, but its exact mode of action remains unknown. The present 1H HR-MAS NMR-based metabolomic study was performed on ovarian cancer cell line A2780, on its cis-Pt resistant variant A2780cisR, and on the cell line HEK-293 treated with 0.03 µM and 0.015 µM of DiRu-1 corresponding to full and half IC50 doses, respectively, to investigate the mode of action of this ruthenium complex. The resulting changes in the metabolic profile of the cell lines were studied using HR-MAS NMR of cell lysates and a subsequent statistical analysis. We show that DiRu-1 in a 0.03 µM dose has significant impact on the levels of a number of metabolites, such as glutamine, glutamate, glutathione, cysteine, lipid, creatine, lactate, and acetate, especially pronounced in the A2780cisR cell line. The IC50/2 dose shows some significant changes, but full IC50 appears to be necessary to observe the full effect. Overall, the metabolic changes observed suggest that redox homeostasis, the Warburg effect, and the lipid metabolism are affected by DiRu-1. View Full-Text
Keywords: ovarian cancer; cytotoxicity; ruthenium complex; HR-MAS NMR; NMR metabolomics; A2780; cis-Pt resistant; metal-based drugs ovarian cancer; cytotoxicity; ruthenium complex; HR-MAS NMR; NMR metabolomics; A2780; cis-Pt resistant; metal-based drugs
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Primasová, H.; Paul, L.E.H.; Diserens, G.; Primasová, E.; Vermathen, P.; Vermathen, M.; Furrer, J. 1H HR-MAS NMR-Based Metabolomics of Cancer Cells in Response to Treatment with the Diruthenium Trithiolato Complex [(p-MeC6H4iPr)2Ru2(SC6H4-p-But)3]+ (DiRu-1). Metabolites 2019, 9, 146.

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    Link: https://www.ebi.ac.uk/metabolights/MTBLS1014
    Description: MTBLS1014: 1H HR-MAS NMR based metabolomics of cancer cells responding to two different doses of the diruthenium trithiolato complex [(p-MeC6H4iPr)2Ru2(SC6H4-p-But)3]+ (DiRu-1)
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