Potential Markers of Cisplatin Treatment Response Unveiled by NMR Metabolomics of Human Lung Cells

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.