1H NMR metabolomics analysis of the effect of dichloroacetate and allopurinol on breast cancers
| Autor: | Vett K. Lloyd, Mohamed Touaibia, Adrian S. Culf, Natalie Lefort, Amy N. Brown, Rodney J. Ouellette, Miroslava Cuperlovic-Culf |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
0303 health sciences
Pyruvate dehydrogenase kinase Chemistry Clinical Biochemistry Pharmaceutical Science Allopurinol Pharmacology 3. Good health Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Metabolomics Cell culture 030220 oncology & carcinogenesis Drug Discovery Cancer cell medicine Extracellular skin and connective tissue diseases Xanthine oxidase Spectroscopy Intracellular 030304 developmental biology medicine.drug |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 93:77-85 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2013.08.017 |
| Popis: | Metabolomics analysis was used to determine the effect of two well known, non-proprietary metabolic modulators, dichloroacetate and allopurinol on breast cancer cell lines. Dichloroacetate, a pyruvate dehydrogenase kinase inhibitor and allopurinol, a xanthine oxidase/dehydrogenase inhibitor, have been previously explored as chemotherapeutics showing potential in some cancer subtypes while at the same time leading to unexpected increase in proliferation in others. In this work, metabolic effects of these drugs, applied singly and in combination, were explored in three different breast cell lines including cancer cells, MDA-MB-231 and MCF-7 and normal control cell line, MCF-10A. The metabolic changes induced by these drugs were monitored by (1)H NMR metabolic profiling. Analyses were performed on complete spectral data as well as quantified metabolic data in intracellular fractions and extracellular media leading to the determination of the most significantly affected metabolites. The effect of dichloroacetate and allopurinol is the most apparent in the metabolic profile of extracellular media. In MCF-7 cells, dichloroacetate treatment is dominant with only a minor observed influence of allopurinol in combined treatment. In MDA-MB-231 cells, both allopurinol and DCA lead to a metabolic shift with the allopurinol change dominating the effect of combined treatment. Results show the power of metabolomics as a tool for fast molecular profiling of drug effects in cells. In summary, treatments of breast cancer cells with DCA and allopurinol result in larger changes in metabolites found in extracellular medium than intracellular pools. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect