Inflammation, Cancer and Oxidative Lipoxygenase Activity are Intimately Linked

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.

Effect of C‐reactive protein/albumin ratio on prognosis in advanced non–small‐cell lung cancer

“…For example, interleukin‐6 can induce CRP and specific acute‐phase response protein, activate STAT3 and NF‐κB, prevent apoptosis and promote tumor cell proliferation . By secreting factors to form inflammatory microenvironments, inflammatory cells can robustly promote tumors …”

Computational Evaluation of Pharmacokinetics and Potential Protein Targets of Ginger (Zingiber officinale)

“…Previous computational study has showed that ginger components could be optimized as lead for the treatment of neurodegenerative diseases, such as Alzheimer's disease, because of its wide spectrum of potential targets which include acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-site amyloid precursor protein cleaving enzyme (BACE-1), human carboxylesterase (hCE-1), and nitric oxide synthase (NOS) among others [24].The lipoxygenases has been reported to have intimately linked activities [21]. The report of Nievergelt et al [17] indicated that 10-shogaol, 1-dehydro-6-gingerdione, and particularly the whole lipophilic ginger extract partially activated the 5-HT1Areceptor (20-60% of maximal activation).…”

In silico and in vitro evaluation of the biological activity of some organicsulfur-containing compounds

“…The roles of the cyclooxygenase enzyme and LOX in the inflammatory process were extensively explored [37][38][39]. It was shown that the metabolism of arachidonic acid generated a host of proinflammatory metabolites.…”