title: 5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumorigenesis.
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.
authors.affiliation: Institute of Pharmaceutical Chemistry/ZAFES, Goethe University Frankfurt Frankfurt, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.forename: Astrid Stefanie
authors.initials: AS
authors.lastname: Fischer
authors.forename: Julia
authors.initials: J
authors.lastname: Metzner
authors.forename: Svenja Dorothea
authors.initials: SD
authors.lastname: Steinbrink
authors.forename: Jessica
authors.initials: J
authors.lastname: Roos
authors.forename: Martin
authors.initials: M
authors.lastname: Ruthardt
authors.forename: Thorsten Jürgen
authors.initials: TJ
authors.lastname: Maier