¹H NMR metabolomics analysis of the effect of dichloroacetate and allopurinol on breast cancers

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DOIResolve DOI: http://doi.org/10.1016/j.jpba.2013.08.017
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TypeArticle
Journal titleJournal of Pharmaceutical and Biomedical Analysis
ISSN0731-7085
AbstractMetabolomics 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 ¹H 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.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationInformation and Communication Technologies; National Research Council Canada
Peer reviewedYes
NPARC number21270499
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Record identifiercf147b86-583f-4699-afa3-d1a8e1cb10d7
Record created2014-02-14
Record modified2016-05-09
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