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Title: Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs
Authors: Martins, Ana S. 
Batista de Carvalho, Ana L. M. 
Marques, Maria Paula M. 
Gil, Ana M
Keywords: metal chelates; human osteosarcoma cells; palladium; platinum; spermine; NMR; metabolomics; endometabolome
Issue Date: 8-Aug-2021
Publisher: MDPI
Project: UIDB/50011/2020 
Centro-01-0145- FEDER-029956 
PhD grant SFRH/BD/ 111576/2015 funded by the European Social Fund of the European Union and national funds FCT/MCTES 
Portuguese National NMR Network (PTNMR), supported by FCT funds as the NMR spectrometer used is part of PTNMR and partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL, and the FCT through PIDDAC) 
Serial title, monograph or event: Molecules
Volume: 26
Issue: 16
Abstract: This paper reports the first metabolomics study of the impact of new chelates Pt2Spm and Pd2Spm (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, Pd2Spm 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.
ISSN: 1420-3049
DOI: 10.3390/molecules26164805
Rights: openAccess
Appears in Collections:FCTUC Química - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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