Abstract
Cancer and inflammation are intimately linked due to specific oxidative processes in the tumor microenvironment. Lipoxygenases are a versatile class of oxidative enzymes involved in arachidonic acid metabolism. An increasing number of arachidonic acid metabolites is being discovered and apart from their classically recognized pro-inflammatory effects, anti-inflammatory effects are also being described in recent years. Interestingly, these lipid mediators are involved in activation of pro-inflammatory signal transduction pathways such as the nuclear factor κB (NF-κB) pathway, which illustrates the intimate link between lipid signaling and transcription factor activation. The identification of the role of arachidonic acid metabolites in several inflammatory diseases led to a significant drug discovery effort around arachidonic acid metabolizing enzymes. However, to date success in this area has been limited. This might be attributed to the lack of selectivity of the developed inhibitors and to a lack of detailed understanding of the functional roles of arachidonic acid metabolites in inflammatory responses and cancer. This calls for a more detailed investigation of the activity of arachidonic acid metabolizing enzymes and development of more selective inhibitors.
Highlights
Inflammation and cancer are closely linked by specific oxidative processes in the tumor microenvironment [1]
Lipoxygenases are a group of oxidative enzymes with a non-heme iron atom in their active site, which are involved in the regulation of inflammatory responses by generation of pro-inflammatory mediators known as leukotrienes or anti-inflammatory mediators known as lipoxins
The activated nuclear factor κB (NF-κB) pathway is involved in the pathogenesis of inflammatory diseases such as asthma, arthritis, inflammatory bowel diseases (IBD) and chronic obstructive pulmonary diseases (COPD) [37,38,39]
Summary
Inflammation and cancer are closely linked by specific oxidative processes in the tumor microenvironment [1]. Oxidative enzymes that are known to play a key role in inflammation are increasingly investigated in connection to cancer. The immune response on the cellular levels is carefully orchestrated by signal transduction pathways such as the nuclear factor κB (NF-κB) pathway. In this review we will discuss the lipid mediators that are produced by lipoxygenases, their role in the regulation of inflammatory responses among others via the NF-κB pathway, their connection with inflammatory diseases and cancer as well as small molecule lipoxygenase inhibitors
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