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)
| Autor: | Ester Primasová, Lydia E. H. Paul, Martina Vermathen, Julien Furrer, Peter Vermathen, Gaëlle Diserens, Hedvika Primasova |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism Physiology 610 Medicine & health Biology A2780 metal-based drugs Biochemistry Article 03 medical and health sciences chemistry.chemical_compound ruthenium complex NMR metabolomics 0302 clinical medicine 540 Chemistry Cytotoxicity Mode of action Molecular Biology cis-Pt resistant Lipid metabolism Glutathione Warburg effect Glutamine 030104 developmental biology ovarian cancer chemistry Cell culture 030220 oncology & carcinogenesis Cancer cell HR-MAS NMR 570 Life sciences biology cytotoxicity |
| Zdroj: | Metabolites Primasova, Hedvika; Paul, Lydia; Diserens, Gaëlle; Primasová, Ester; Vermathen, Peter; Vermathen, Martina; Furrer, Julien (2019). 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, 9(7), p. 146. MDPI 10.3390/metabo9070146 Volume 9 Issue 7 |
| ISSN: | 2218-1989 |
| DOI: | 10.3390/metabo9070146 |
| Popis: | 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 µ M and 0.015 µ M 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 µ M 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. |
| Databáze: | OpenAIRE |
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