Eicosanoids and cancer

Abstract

Eicosanoids are 20-carbon bioactive lipids derived from the metabolism of polyunsaturated fatty acids, which can modulate various biological processes including cell proliferation, adhesion and migration, angiogenesis, vascular permeability and inflammatory responses. In recent years, studies have shown the importance of eicosanoids in the control of physiological and pathological processes associated with several diseases, including cancer. The polyunsaturated fatty acid predominantly metabolized to generate 2-series eicosanoids is arachidonic acid, which is the major n-6 polyunsaturated fatty acid found in animal fat and in the occidental diet. The three main pathways responsible for metabolizing arachidonic acid and other polyunsaturated fatty acids to generate eicosanoids are the cyclooxygenase, lipoxygenase and P450 epoxygenase pathways. Inflammation plays a decisive role in various stages of tumor development including initiation, promotion, invasion and metastasis. This review will focus on studies that have investigated the role of prostanoids and lipoxygenase-derived eicosanoids in the development and progression of different tumors, highlighting the findings that may provide insights into how these eicosanoids can influence cell proliferation, cell migration and the inflammatory process. A better understanding of the complex role played by eicosanoids in both tumor cells and the tumor microenvironment may provide new markers for diagnostic and prognostic purposes and identify new therapeutic strategies in cancer treatment.

Resveratrol Action on Lipid Metabolism in Cancer

“…The release of ARA from the cell membrane is initiated by phospholipase A2 (PLA2) and, thereafter, converted to eicosanoids [154]. Eicosanoids, including prostaglandins and leukotrienes, are products of local cell type-specific metabolism of ARA and form an important class of bioactive lipid mediators, playing critical roles in diverse physiological and pathological processes, such as inflammation and cancer [155,156,157,158]. In cancer patients, the level of PLA2 elevates significantly [159,160,161].…”

“…This group of molecules encompasses a wide array of hormones which build the different classes, such as prostaglandins, thromboxanes, leukotrienes, lipoxins, epoxyeicosatrienoic acids, etc. Above all, the importance of prostanoid and leukotriene biosynthetic pathway in carcinogenesis and chronic inflammation is supported by a plenty of in vivo and clinical studies [156,157,181,182]. Prostaglandins and leukotrienes promote tumor growth by regulating tumor epithelial cells themselves and controlling the complex interactions between transformed epithelial cells and surrounding stromal cells to establish a tumor microenvironment that facilitates tumor-associated angiogenesis and evades attack by the immune system [182].…”

Eicosanoids in carcinogenesis

“…Detailed knowledge of various pathways with its functional implications is needed and "…metabolic network by using systems biology approaches, should be strongly encouraged" [459]. Furthermore, this needs to include reaction specifity information of regulatory mediators impacting the biological activity of various enzymes and poteins including its dynamic changes [460][461][462][463].…”

EP3 Is an Independent Prognostic Marker Only for Unifocal Breast Cancer Cases

“…The prostanoid receptors EP 1-4 are divided into groups based on the type of G protein, through which they evoke cellular responses. EP1 unfolds its effect through Ca 2+ dependent activation by Gq proteins [5]. EP2 and EP4 are coupled to Gs (G stimulatory) proteins, whose activation stimulates the production of cAMP.…”

“…EP2 and EP4 are coupled to Gs (G stimulatory) proteins, whose activation stimulates the production of cAMP. Prostaglandin receptor 3 (EP3), which exists in eight isoforms, mostly is coupled to a Gi (inhibitory) protein, whose activation reduces the cAMP production [5,6]. When existing in another isotype EP3 also binds to a Gs (stimulatory) protein, which results in increased cAMP levels [7].…”