NMR-Based Metabolomics in Metal-Based Drug Research

Abstract

Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. In particular, NMR spectroscopy has shown great potential as a detection technique, mainly for the ability to detect multiple (10s to 100s) metabolites at once without separation. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. As expected, these studies are mainly focused on platinum complexes, but some palladium and ruthenium compounds are also under investigation. The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based, in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments.

Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent

“…The deleterious effects of Pt-drugs have triggered the development of complexes [ 9 , 16 ] with transition-metal centers such as palladium(II), gold(I)/(III), and ruthenium(II)/(III) [ 8 , 17 , 18 ]. Pd(II) has been recognized as one of the best candidates due to its physical-chemical similarities to Pt(II) [ 8 , 14 ].…”

“…Further metabolic perturbations produced in vitro and in vivo (both locally (tissues) and systemically (biofluids)) are detectable by metabolomics and may pave the way for defining possible new markers of drug toxicity, efficacy, or resistance [ 46 , 47 ]. Unlike for cisplatin [ 48 , 49 , 50 ], the effects of Pd(II)-complexes have rarely been evaluated by metabolomics [ 16 ], to the best of our knowledge, with a single report comprising the impact of Pd 2 Spm complex on human osteoblasts (HOb) and osteosarcoma (MG-63) cells using nuclear magnetic resonance (NMR)-based metabolomics [ 51 ].…”

1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages

“…During these years, the clear role of specific metabolic pathways in driving pro-tumorigenic events including tumor growth, chemoresistance and plasticity, is emerged [19][20][21][22][23][24]. An over-expression of metabolic genes regulating glycolysis, aminoacyl-tRNA biosynthesis, pyrimidine biosynthesis, purine biosynthesis and pentose phosphate pathway characterize tumor tissues compared to normal samples, thus highlighting the hypothesis of a specific metabolic signature at the tumor level [25].…”

Metabolic Aspects of Palladium(II) Potential Anti-Cancer Drugs

“…In this case, this approach revealed that Pd 2 Spm can impact differently on cell metabolism (of both cancer and healthy cells), depending on whether it is administered alone or combined with other drugs. In fact, the promise of such strategies in revealing hidden features of cellular response to metal complexes with potential anti-cancer action has been recently reviewed, giving particular emphasis to NMR as the chosen analytical technique ( 32 ).…”