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Lookup NU author(s): Dr Frida Ponthan
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The metabolism of arachidonic acid by the cyclooxygenase (COX) or lipoxygenase (LO) pathways generates eicosanoids that have been implicated in the pathogenesis of a variety of human diseases, including cancer. In this study, we examined the expression and significance of components within the 5-LO pathway in human neuroblastoma, an embryonal tumor of the sympathetic nervous system. High expression of 5-LO, 5-LO-activating protein (FLAP), leukotriene A4 hydrolase, leukotriene C4 synthase, and leukotriene receptors was detected in a majority of primary neuroblastoma tumors and all cell lines investigated. Expression of 5-LO and FLAP was evident in tumor cells but not in nonmalignant adrenal medulla where neuroblastomas typically arise. Moreover, neuroblastoma cells produce leukotrienes, and stimulation of neuroblastoma cells with leukotrienes increased neuroblastoma cell viability. Inhibitors of 5-LO (AA-861), FLAP (MK-886), or the leukotriene receptor antagonist montelukast inhibited neuroblastoma cell growth by induction of G1-cell cycle arrest and apoptosis. Similarly, specific 5-LO and leukotriene receptor silencing by small interfering RNA decreased neuroblastoma cell growth. These findings provide new insights into the pathobiology of neuroblastoma, and the use of leukotriene pathway inhibitors as a novel adjuvant therapy for children with neuroblastoma warrants further consideration. © FASEB.
Author(s): Sveinbjornsson B, Rasmuson A, Baryawno N, Wan M, Pettersen I, Ponthan F, Orrego A, Haeggstrom JZ, Johnsen JI, Kogner P
Publication type: Article
Publication status: Published
Journal: The FASEB Journal
Year: 2008
Volume: 22
Issue: 10
Pages: 3525-3536
ISSN (print): 0892-6638
ISSN (electronic): 1530-6860
Publisher: Federation of American Societies for Experimental Biology
URL: http://dx.doi.org/10.1096/fj.07-103457
DOI: 10.1096/fj.07-103457
PubMed id: 18591367
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