Potential Markers of Cisplatin Treatment Response Unveiled by NMR Metabolomics of Human Lung Cells
authors Duarte, IF; Ladeirinha, AF; Lamego, I; Gil, AM; Carvalho, L; Carreira, IM; Melo, JB
nationality International
journal MOLECULAR PHARMACEUTICS
author keywords A549 lung cells; cisplatin; HRMAS NMR; metabolic profile; metabolomics
keywords VISIBLE MOBILE LIPIDS; CANCER CELLS; APOPTOTIC CELLS; LEUKEMIA-CELLS; GENE-THERAPY; GLIOMA-CELLS; TUMOR-CELLS; H-1-NMR; SPECTROSCOPY; DEATH
abstract In this work, H-1 high resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy was used to characterize the variations in the metabolome (small metabolites and mobile lipids) of A549 human lung cells in response to exposure to the alkylating drug cisplatin. Multivariate analysis and signal integration of spectral data were carried out to unveil exposure-induced effects and follow their time course. Parallel and strongly correlated increases in lipids (particularly unsaturated triglycerides) and nucleotide sugars (particularly uridine diphosphate N-acetylglucosamine) were found in cisplatin-treated cells, highlighting these compounds as potential biomarkers of treatment response. Other significant changes upon drug exposure comprised an increase in sorbitol and decreases in niacinamide and several amino acids (glutamine, alanine, lysine, methionine, citrulline, phenylalanine and tyrosine). These results show that in vitro NMR metabolomics is a powerful tool for detecting variations in a range of intracellular compounds upon drug exposure, thus offering the possibility of identifying candidate metabolite markers for in vivo monitoring of tumor responsiveness to treatment.
publisher AMER CHEMICAL SOC
issn 1543-8384
year published 2013
volume 10
issue 11
beginning page 4242
ending page 4251
digital object identifier (doi) 10.1021/mp400335k
web of science category Medicine, Research & Experimental; Pharmacology & Pharmacy
subject category Research & Experimental Medicine; Pharmacology & Pharmacy
unique article identifier WOS:000326669400029
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journal impact factor 4.556
5 year journal impact factor 4.785
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