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.
keywords
HUMAN BREAST-CANCER; PLATINUM COMPLEXES; COLORIMETRIC ASSAY; ANTICANCER AGENTS; DNA INTERACTIONS; ANTITUMOR DRUGS; CARCINOMA CELLS; TUMOR-CELLS; CISPLATIN; PALLADIUM(II)
subject category
Biochemistry & Molecular Biology
authors
Lamego, I; Marques, MPM; Duarte, IF; Martins, AS; Oliveira, H; Gil, AM
our authors
Ana Maria Pissarra Coelho Gil
Associate Professor with Aggregation
Ana Sofia da Costa Martins
PhD Student
Helena Oliveira
Post-Doc Fellowship
Inês Dias Lamego
PhD Student
Iola Melissa Fernandes Duarte
Principal Researcheracknowledgements
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 "Molecular Physical-Chemistry", University of Coimbra), PTDC/SAL-BEB/66896/2006, SFRH/BD/63916/2009, SFRH/BD/111576/2015, and SFRH/BPD/111736/2015 grants and from the Portuguese National NMR Network (RNRMN). We thank the Associate Laboratory IBMC-INEB for kindly providing the MG-63 cell line, and I.F.D. acknowledges FCT/MCTES for a research contract under the "Investigador FCT" 2014 Program.