Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs
authors Martins, AS; de Carvalho, ALMB; Marques, MPM; Gil, AM
nationality International
journal MOLECULES
author keywords metal chelates; human osteosarcoma cells; palladium; platinum; spermine; NMR; metabolomics; endometabolome
keywords BIOGENIC POLYAMINES; CISPLATIN; COMPLEXES; PROFILE; NMR; IMPACT; CHEMOTHERAPY; GLUTATHIONE; DOXORUBICIN; SPERMIDINE
abstract This paper reports the first metabolomics study of the impact of new chelates Pt(2)Spm and Pd(2)Spm (Spm = Spermine) on human osteosarcoma cellular metabolism, compared to the conventional platinum drugs cisplatin and oxaliplatin, in order to investigate the effects of different metal centers and ligands. Nuclear Magnetic Resonance metabolomics was used to identify meaningful metabolite variations in polar cell extracts collected during exposure to each of the four chelates. Cisplatin and oxaliplatin induced similar metabolic fingerprints of changing metabolite levels (affecting many amino acids, organic acids, nucleotides, choline compounds and other compounds), thus suggesting similar mechanisms of action. For these platinum drugs, a consistent uptake of amino acids is noted, along with an increase in nucleotides and derivatives, namely involved in glycosylation pathways. The Spm chelates elicit a markedly distinct metabolic signature, where inverse features are observed particularly for amino acids and nucleotides. Furthermore, Pd(2)Spm prompts a weaker response from osteosarcoma cells as compared to its platinum analogue, which is interesting as the palladium chelate exhibits higher cytotoxicity. Putative suggestions are discussed as to the affected cellular pathways and the origins of the distinct responses. This work demonstrates the value of untargeted metabolomics in measuring the response of cancer cells to either conventional or potential new drugs, seeking further understanding (or possible markers) of drug performance at the molecular level.
publisher MDPI
isbn 1420-3049
year published 2021
volume 26
issue 16
digital object identifier (doi) 10.3390/molecules26164805
web of science category 15
subject category Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
unique article identifier WOS:000689992900001
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journal analysis (jcr 2019):
journal impact factor 3.267
5 year journal impact factor 3.589
category normalized journal impact factor percentile 56.714
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