Metabolic Markers of MG-63 Osteosarcoma Cell Line Response to Doxorubicin and Methotrexate Treatment: Comparison to Cisplatin
authors Lamego, I; Duarte, IF; Marques, MPM; Gil, AM
nationality International
journal JOURNAL OF PROTEOME RESEARCH
author keywords osteosarcoma; MG-63 cell; line; cisplatin; doxorubicin; methotrexate; cancer; chemotherapy; metabolomics; NMR spectroscopy
keywords MAGNETIC-RESONANCE-SPECTROSCOPY; OF-THE-ART; K562 CELLS; MASS-SPECTROMETRY; INDUCED APOPTOSIS; VISIBLE LIPIDS; LEUKEMIA-CELLS; CANCER CELLS; TUMOR-CELLS; H-1-NMR
abstract A high resolution magic angle spinning NMR metabolomics study of the effects of doxorubicin (DOX), methotrexate (MTX) and cisplatin (cDDP) on MG-63 cells is presented and unveils the cellular metabolic adaptations to these drugs, often used together in clinical protocols. Although cDDP-treated cells were confirmed to undergo extensive membrane degradation accompanied by increased neutral lipids, DOX- and MTX-treated cells showed no lipids increase and different phospholipid signatures, which suggests that (i) DOX induces significant membrane degradation, decreased membrane synthesis, and apparent inhibition of de novo lipid synthesis, and (ii) MTX induces decreased membrane synthesis, while no membrane disruption or de novo lipid synthesis seem to occur. Nucleotide signatures were in apparent agreement with the different drug action mechanisms, a link having been found between UDP-GlcNAc and the active pathways of membrane degradation and energy metabolism, for cDDP and DOX, with a relation to oxidative state and DNA degradation, for cDDP. Correlation studies unveiled drug-specific antioxidative signatures, which pinpointed m- and s-inositols, taurine, glutamate/glutamine, and possibly creatine as important in glutathione metabolism. These results illustrate the ability of NMR metabolomics to measure cellular responses to different drugs, a first step toward understanding drug synergism and the definition of new biomarkers of drug efficacy.
publisher AMER CHEMICAL SOC
issn 1535-3893
year published 2014
volume 13
issue 12
beginning page 6033
ending page 6045
digital object identifier (doi) 10.1021/pr500907d
web of science category Biochemical Research Methods
subject category Biochemistry & Molecular Biology
unique article identifier WOS:000346039400066
link 25382592
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journal impact factor 4.074
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