Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs
This paper reports the first metabolomics study of the impact of new chelates Pt<sub>2</sub>Spm and Pd<sub>2</sub>Spm (Spm = Spermine) on human osteosarcoma cellular metabolism, compared to the conventional platinum drugs cisplatin and oxaliplatin, in order to investigate the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/16/4805 |
| _version_ | 1797522678287958016 |
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| author | Ana S. Martins Ana L. M. Batista de Carvalho Maria P. M. Marques Ana M. Gil |
| author_facet | Ana S. Martins Ana L. M. Batista de Carvalho Maria P. M. Marques Ana M. Gil |
| author_sort | Ana S. Martins |
| collection | DOAJ |
| description | This paper reports the first metabolomics study of the impact of new chelates Pt<sub>2</sub>Spm and Pd<sub>2</sub>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<sub>2</sub>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. |
| first_indexed | 2024-03-10T08:32:51Z |
| format | Article |
| id | doaj.art-0fc8a2fe430243e696dfecb0db0a1205 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:32:51Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0fc8a2fe430243e696dfecb0db0a12052023-11-22T08:52:15ZengMDPI AGMolecules1420-30492021-08-012616480510.3390/molecules26164805Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New DrugsAna S. Martins0Ana L. M. Batista de Carvalho1Maria P. M. Marques2Ana M. Gil3CICECO—Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, PortugalUnidade de I&D Química-Física Molecular, Department of Chemistry, University of Coimbra, Rua Larga, 300-535 Coimbra, PortugalUnidade de I&D Química-Física Molecular, Department of Chemistry, University of Coimbra, Rua Larga, 300-535 Coimbra, PortugalCICECO—Aveiro Institute of Materials (CICECO/UA), Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, PortugalThis paper reports the first metabolomics study of the impact of new chelates Pt<sub>2</sub>Spm and Pd<sub>2</sub>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<sub>2</sub>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.https://www.mdpi.com/1420-3049/26/16/4805metal chelateshuman osteosarcoma cellspalladiumplatinumspermineNMR |
| spellingShingle | Ana S. Martins Ana L. M. Batista de Carvalho Maria P. M. Marques Ana M. Gil Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs Molecules metal chelates human osteosarcoma cells palladium platinum spermine NMR |
| title | Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs |
| title_full | Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs |
| title_fullStr | Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs |
| title_full_unstemmed | Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs |
| title_short | Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs |
| title_sort | response of osteosarcoma cell metabolism to platinum and palladium chelates as potential new drugs |
| topic | metal chelates human osteosarcoma cells palladium platinum spermine NMR |
| url | https://www.mdpi.com/1420-3049/26/16/4805 |
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