• Home
  • Search Results
  • LC-based targeted metabolomics analysis of nucleotides and identification of biomarkers associated with chemotherapeutic drugs in cultured cell models.

LC-based targeted metabolomics analysis of nucleotides and identification of biomarkers associated with chemotherapeutic drugs in cultured cell models.

Anti-cancer drugs (2014-03-29)
Xi Liu, Chen-chen Zhang, Zheng Liu, Lan Wei, Yan-jie Liu, Jing Yu, Li-xin Sun
ABSTRACT

Treatment of mammalian cells with chemotherapeutic drugs can result in perturbations of nucleotide pools. Monitoring these perturbations in cultured tumor cells from human sources is useful for assessment of the effect of drug therapy and a better understanding of the mechanism of action of these drugs. In this study, three classes of chemotherapeutic drugs with different mechanisms of action were used in the development of drug-treated cell models. The LC-based targeted metabolomics analysis of nucleotides in cells of the control group and the drug-treated group was carried out. Several data processing methods were combined for the identification of potential biomarkers associated with the action of drugs, including one-way analysis of variance, principal component analysis, and receiver operating characteristic curves. Intriguingly, tumor cells of both the control group and the drug-treated groups can be distinguished from each other, and several variables were recognized as potential biomarkers, such as ATP, GMP, and UDP for antimetabolite agents, ATP, GMP, and CTP for DNA-damaging agents, as well as GMP, ATP, UDP, and GDP for the mitotic spindle agents. Further validation of the potential biomarkers was performed using the receiver operating characteristic curve. Considering their corresponding area under the curve, which was larger than 0.9, it can be concluded that GMP and ATP are the best potential biomarkers for DNA-damaging drugs, as well as GMP, ATP, and UDP for the other two classes of drugs. This limited nucleotide approach cannot completely distinguish the mechanisms of the nine drugs, but it provides preliminary evidence for the role of pharmacometabolomics in the preclinical development of drugs at least.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, ReagentPlus®, ≥99.5%
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Cytidine 5′-triphosphate disodium salt, ≥95%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Supelco
Dimethyl sulfoxide, analytical standard
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Cytidine 5′-triphosphate disodium solution, HPLC purified, aqueous solution for RNA polymerase transcription
Sigma-Aldrich
Dimethyl sulfoxide solution, 50 wt. % in H2O