title: NMR metabolomics analysis of the effects of 5-lipoxygenase inhibitors on metabolism in glioblastomas.
abstract: Changes 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.
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, Canada.
authors.forename: Pier
authors.initials: P
authors.lastname: Morin
authors.forename: Dean
authors.initials: D
authors.lastname: Ferguson
authors.forename: Luc M
authors.initials: LM
authors.lastname: LeBlanc
authors.forename: Martin J G
authors.initials: MJ
authors.lastname: Hébert
authors.forename: Aurélie F
authors.initials: AF
authors.lastname: Paré
authors.forename: Jacques
authors.initials: J
authors.lastname: Jean-François
authors.forename: Marc E
authors.initials: ME
authors.lastname: Surette
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touaibia
authors.forename: Miroslava
authors.initials: M
authors.lastname: Cuperlovic-Culf
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002109:Caffeic Acids / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015289:Leukotrienes / Q000096:biosynthesis; D050356:Lipid Metabolism / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome; D055432:Metabolomics; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D025341:Principal Component Analysis
chemical_list: D000970:Antineoplastic Agents; D002109:Caffeic Acids; D016166:Free Radical Scavengers; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; C063449:zileuton; D006918:Hydroxyurea