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Review
. 2016 Jul 16;4(7):155-64.
doi: 10.12998/wjcc.v4.i7.155.

Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

Kazuki Moro  1 , Masayuki Nagahashi  1 , Rajesh Ramanathan  1 , Kazuaki Takabe  1 , Toshifumi Wakai  1
Affiliations
Review

Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

Kazuki Moro et al. World J Clin Cases. .

Abstract

Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers.

Keywords: Anti-inflammatory lipid mediators; Cancer; Inflammatory diseases; Omega three polyunsaturated fatty acids; Resolvin.

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Figures

Figure 1
Figure 1
A course of acute inflammation with two phases: The onset phase and the resolving phase. Acute inflammation is caused by stresses such as tissue injuries, microbial infections or surgical intervention. There are two phases in acute inflammation: The onset phase, and the resolving phase. Usually, the inflammation is resolved through these phases. When the inflammation is not resolved, it develops diseases with chronic inflammation. For instance, inflammation in stomach caused by microbial infections follow a course of the two phases in acute inflammation. When the acute inflammation is not resolved through the resolving phase, it develops chronic gastritis. PG: Prostaglandins; LT: Leukotrienes; TNF: Tumor necrosis factor; S1P: Sphingosine-1-phosphate; LPA: Lysophosphatidic acid.
Figure 2
Figure 2
Classification of lipid mediators of inflammation. Lipid mediators are classified with fatty acids, phospholipids and others. Among the fatty acids, eicosanoids are the derivatives of polyunsaturated fatty acids (PUFA), which are present in dietary sources, such as fish oil (ω-3 PUFA) and vegetable oil (ω-6 PUFA). ω-6 PUFA generates prostaglandins (PG), leukotrienes (LT), thromboxanes (Tx) and lipoxins (Lx). Resolvin originates from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are components of ω-3 PUFA. Resolvin derived from EPA and DHA are termed resolvin E (RvE) and resolvin D (RvD) series, respectively, both of which act as pro-resolving mediators. Phospholipids including sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) and others including ceramides and ceramide-1-phosphate (C1P) usually act as pro-inflammatory mediators. Red: Pro-inflammatory mediators; Blue: Pro-resolving mediators.
Figure 3
Figure 3
Classification of resolvins. Resolvins are biosynthesized from ω-3 polyunsaturated fatty acids (PUFA) by specific enzymes including lipoxygenase (LOX). Resolvin E (RvE) is endogenously produced from eicosapentaenoic acid (EPA) during endothelial cell-leukocyte interaction. RvE1 and RvE2 are biosynthesized through two different pathways via cytochrome P450-driven oxygenation of EPA or via aspirin-acetylated cyclooxygenase 2 (COX-2). RvE3 is generated via the 12/15-LOX pathway. In addition, resolvin D (RvD) is biosynthesized from docosahexaenoic acid (DHA) via 15/5-LOX within vascular endothelial cells. To date, six members of this family has been identified RvD1-6. Also, RvD is also biosynthesized via aspirin-acetylated COX-2, and we call aspirin triggered RvD (AT-RvD).
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