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title Impact of the Pd(2)Spermine Chelate on Osteosarcoma Metabolism: An NMR Metabolomics Study
authors Lamego, I; Marques, MPM; Duarte, IF; Martins, AS; Oliveira, H; Gil, AM
author full name Lamego, Ines; Marques, M. Paula M.; Duarte, Iola F.; Martins, Ana S.; Oliveira, Helena; Gil, Ana M.
title Impact of the Pd(2)Spermine Chelate on Osteosarcoma Metabolism: An NMR Metabolomics Study
nationality internacional
source JOURNAL OF PROTEOME RESEARCH
language English
document type Article
author keywords palladium anticancer drugs; osteosarcoma; osteoblasts; metabolomics; NMR
keywords plus HUMAN BREAST-CANCER; PLATINUM COMPLEXES; COLORIMETRIC ASSAY; ANTICANCER AGENTS; DNA INTERACTIONS; ANTITUMOR DRUGS; CARCINOMA CELLS; TUMOR-CELLS; CISPLATIN; PALLADIUM(II)
abstract A metabolomics study of Pd(2)Sperrnine(Spm) on osteosarcoma MG-63 and oSteoblastic HOb cells is presented to assess the impact of the potential palladium drug on cell metabolism compared with cisplatin (cDDP). Despite its higher cytotoxicity, Pd(2)Spm indticed lower (and reversible) metabolic impact on MG-63 cells and the absence of apoptosis; conversely, it induced significant deviations in osteoblastic:amino acid metabolism. However, when in combination with doxorubicin and methotrexate, Pd(2)Spm induced strong metabolic deviations on lipids, choline compounds, amino acids, nucleotides, and compounds related to antioxidative.mechanisms (e.g., glutathione,,inositol, hypoxanthine), similarly to the cDDP cocktail. Synergetic effects included triggering of lipid biosynthesis by Pd(2)Spm in the presence of doxorubicin (and reinforced by methotrexate) and changes in the glycosylation substrate uridine diphosphate acetylgalactosamine and methionine and serine metabolisms. This work provides promising results related to the impact of Pd(2)Spm on osteosarcoma cellular metabolism, particularly in drug combination protocols. Lipid metabolism, glycosylation, and amino acid metabolisms emerge as relevant features for targeted studies to further understand a potential anticancer mechanism of combined Pd(2)Spm.
author address [Lamego, Ines; Duarte, Iola F.; Martins, Ana S.; Gil, Ana M.] Univ Aveiro, Dept Chem, P-3810 Aveiro, Portugal; [Lamego, Ines; Duarte, Iola F.; Martins, Ana S.; Gil, Ana M.] Univ Aveiro, CICECO Aveiro Inst Mat CICECO UA, P-3810 Aveiro, Portugal; [Lamego, Ines; Marques, M. Paula M.] Univ Coimbra, R&D Unit Mol Phys Chem, P-3000213 Coimbra, Portugal; [Marques, M. Paula M.] Univ Coimbra, Fac Sci & Technol, Dept Life Sci, P-3000213 Coimbra, Portugal; [Oliveira, Helena] Univ Aveiro, Dept Biol, P-3810 Aveiro, Portugal; [Oliveira, Helena] Univ Aveiro, CESAM, P-3810 Aveiro, Portugal
reprint address Gil, AM (reprint author), Univ Aveiro, Dept Chem, P-3810 Aveiro, Portugal.; Gil, AM (reprint author), Univ Aveiro, CICECO Aveiro Inst Mat CICECO UA, P-3810 Aveiro, Portugal.
e-mail address agil@ua.pt
researcherid number Oliveira, Helena/M-5068-2013; Duarte, Iola/H-5505-2013
orcid number Oliveira, Helena/0000-0002-4673-0696; Duarte, Iola/0000-0003-4289-9256; Gil, Ana/0000-0003-3766-4364; Marques, Maria Paula/0000-0002-8391-0055; Martins, Ana Sofia/0000-0001-6865-5853
funding agency and grant number FCT/MEC [FCT/UID/CTM/ 50011/2013]; Portuguese Foundation for Science and Technology [PTDC/QEQMED/1890/2014, 3599]; European Community Fund FEDER [3599-PPCDT]; FCT funds [UID/MULTI/00070/2013, PTDC/SAL-BEB/66896/2006, SFRH/BD/63916/2009, SFRH/BD/111576/2015, SFRH/BPD/111736/2015]; Portuguese National NMR Network (RNRMN); FEDER
funding text This work was developed within the scope of the project CICECO-Aveiro Institute of Materials (ref. FCT/UID/CTM/ 50011/2013), financed by national funds through the FCT/MEC and cofinanced by FEDER under the PT2020 Partnership Agreement. We acknowledge financial support from the Portuguese Foundation for Science and Technology: PTDC/QEQMED/1890/2014, within Project 3599, to Promote Scientific Production and Technological Development, as well as the formation of thematic networks (3599-PPCDT), jointly financed by the European Community Fund FEDER. FCT funds are also acknowledged from UID/MULTI/00070/2013 (R&D Group
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cited reference count 49
times cited 1
total times cited count (wos, bci, and cscd) 1
publisher AMER CHEMICAL SOC
publisher city WASHINGTON
publisher address 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
issn 1535-3893
29-character source abbreviation J PROTEOME RES
iso source abbreviation J. Proteome Res.
publication date APR
year published 2017
volume 16
issue 4
beginning page 1773
ending page 1783
digital object identifier (doi) 10.1021/acs.jproteome.7b00035
subject category 11
document delivery number Biochemical Research Methods
unique article identifier Biochemistry & Molecular Biology