TY  - JOUR
A1  - Steinhilber, Dieter
A1  - Fischer, Astrid Stefanie
A1  - Metzner, Julia
A1  - Steinbrink, Svenja Dorothea
A1  - Roos, Jessica
A1  - Ruthardt, Martin
A1  - Maier, Thorsten Jürgen
T1  - 5-Lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis
T2  - Frontiers in Pharmacotherapy of Inflammation
N2  - 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
KW  - leukotriene
KW  - apoptosis
KW  - cell proliferation
KW  - mitogenic effects
KW  - cytotoxicity
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/20670
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-89103
N1  - 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.
VL  - 1
IS  - 143
ER  -