期刊
JOURNAL OF PROTEOME RESEARCH
卷 12, 期 5, 页码 2165-2176出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr400026q
关键词
Drug discovery; NMR Metabolomics; Caffeic acid phenethyl ester; 5-lipoxygenase inhibitors; Glioblastoma multiforme; Antioxidant and antiradical activity
资金
- Beatrice Hunter Cancer Research Institute
- Brain Tumour Foundation of Canada
- New Brunswick Health Research Foundation
- CFI through the Infrastructure Operating Fund (IOF)
- Canada Research Chairs Program
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.
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