NMR metabolomics analysis of the effects of 5-lipoxygenase inhibitors on metabolism in glioblastomas

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DOIResolve DOI: http://doi.org/10.1021/pr400026q
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TypeArticle
Journal titleJournal of Proteome Research
ISSN1535-3893
Volume12
Issue5
Pages21652176; # of pages: 12
SubjectDrug discovery; NMR Metabolomics; Caffeic acid phenethyl ester; 5-lipoxygenase inhibitors; Glioblastoma multiforme; Antioxidant and antiradical activity
AbstractChanges across metabolic networks are emerging as an integral part of cancer development and progression. Increasing comprehension of the importance of metabolic processes as well as metabolites in cancer is stimulating exploration of novel, targeted treatment options. Arachidonic acid (AA) is a major component of phospholipids. Through the cascade catalyzed by cyclooxygenases and lipoxygenases, AA is also a precursor to cellular signaling molecules as well as molecules associated with a variety of diseases including cancer. 5-Lipoxygenase catalyzes the transformation of AA into leukotrienes (LT), important mediators of inflammation. High-throughput analysis of metabolic profiles was used to investigate the response of glioblastoma cell lines to treatment with 5-lipoxygenase inhibitors. Metabolic profiling of cells following drug treatment provides valuable information about the response and metabolic alterations induced by the drug action and give an indication of both on-target and off-target effects of drugs. Four different 5-lipoxygenase inhibitors and antioxidants were tested including zileuton, caffeic acid, and its analogues caffeic acid phenethyl ester and caffeic acid cyclohexethyl ester. A NMR approach identified metabolic signatures resulting from application of these compounds to glioblastoma cell lines, and metabolic data were used to develop a better understanding of the mode of action of these inhibitors.
Publication date
LanguageEnglish
AffiliationInformation and Communication Technologies; National Research Council Canada
Peer reviewedYes
NPARC number21270517
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Record identifierece1ba28-0395-4f13-9c87-f011aaea97c8
Record created2014-02-14
Record modified2016-05-09
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