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

Steinhilber, Dieter, Fischer, Astrid Stefanie, Metzner, Julia, Steinbrink, Svenja Dorothea, Roos, Jessica, Ruthardt, Martin ORCID: https://orcid.org/0000-0003-1021-3811 and Maier, Thorsten Jürgen 2010. 5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis. Frontiers in Pharmacology 1 (143) 10.3389/fphar.2010.00143

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Abstract

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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Frontiers Media
ISSN:	1663-9812
Date of Acceptance:	10 December 2010
Last Modified:	22 Feb 2024 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/166081

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