5-Lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis

Leukotrienes constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body of evidence supports an acute role for 5-LO products already during the earliest stages of pancreatic
Leukotrienes constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body of evidence supports an acute role for 5-LO products already during the earliest stages of pancreatic, prostate, and colorectal carcinogenesis. Several pieces of experimental data form the basis for this hypothesis and suggest a correlation between 5-LO expression and tumor cell viability. First, several independent studies documented an overexpression of 5-LO in primary tumor cells as well as in established cancer cell lines. Second, addition of 5-LO products to cultured tumor cells also led to increased cell proliferation and activation of anti-apoptotic signaling pathways. 5-LO antisense technology approaches demonstrated impaired tumor cell growth due to reduction of 5-LO expression. Lastly, pharmacological inhibition of 5-LO potently suppressed tumor cell growth by inducing cell cycle arrest and triggering cell death via the intrinsic apoptotic pathway. However, the documented strong cytotoxic off-target effects of 5-LO inhibitors, in combination with the relatively high concentrations of 5-LO products needed to achieve mitogenic effects in cell culture assays, raise concern over the assignment of the cause, and question the relationship between 5-LO products and tumorigenesis. Keywords: leukotriene, apoptosis, cell proliferation, mitogenic effects, cytotoxicity
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Metadaten
Author:Dieter Steinhilber, Astrid Stefanie Fischer, Julia Metzner, Svenja Dorothea Steinbrink, Jessica Roos, Martin Ruthardt, Thorsten Jürgen Maier
URN:urn:nbn:de:hebis:30-89103
Document Type:Article
Language:English
Date of Publication (online):2011/01/12
Year of first Publication:2010
Publishing Institution:Univ.-Bibliothek Frankfurt am Main
Release Date:2011/01/12
Tag:apoptosis ; cell proliferation ; cytotoxicity; leukotriene ; mitogenic effects
Note:
Copyright © 2010 Steinhilber, Fischer, Metzner, Steinbrink, Roos, Ruthardt and Maier. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Source:Frontiers in Pharmacotherapy of Inflammation, 1:143 ; doi: 10.3389/fphar.2010.00143 ; http://www.frontiersin.org/pharmacotherapy_of_inflammation/10.3389/fphar.2010.00143/full
HeBIS PPN:231027915
Institutes:Biochemie und Chemie
Medizin
Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License Logo Veröffentlichungsvertrag für Publikationen

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