Breaking the cycle: the role of omega-3 polyunsaturated fatty acids in inflammation-driven cancers

2014 ◽  
Vol 92 (5) ◽  
pp. 321-328 ◽  
Author(s):  
William L. Patterson ◽  
Philippe T. Georgel
Keyword(s):  
Fatty Acids ◽  
Transcription Factors ◽  
Polyunsaturated Fatty Acids ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Immune Cells ◽  
Signaling Molecules ◽  
Inflammatory Signaling ◽  
Vast Number ◽  
Anti Inflammatory

Chronic inflammation is a cyclical, self-stimulating process. Immune cells called to sites of inflammation release pro-inflammatory signaling molecules that stimulate activation of inducible enzymes and transcription factors. These enzymes and transcription factors then stimulate production of signaling molecules that attract more immune cells and induce more enzymatic and transcriptional activity, creating a perpetual loop of inflammation. This self-renewing pool of inflammatory stimuli makes for an ideal tumor microenvironment, and chronic inflammation has been linked to oncogenesis, tumor growth, tumor cell survival, and metastasis. Three protein pathways in particular, nuclear factor kappa B (NF-kB), cyclooxygenase (COX), and lipoxygenase (LOX), provide excellent examples of the cyclical, self-renewing nature of chronic inflammation-driven cancers. NF-kB is an inducible transcription factor responsible for the expression of a vast number of inflammation and cancer related genes. COX and LOX convert omega-6 (n-6) and omga-3 (n-3) polyunsaturated fatty acids (PUFA) into pro- and anti-inflammatory signaling molecules. These signaling molecules stimulate or repress activity of all three of these pathways. In this review, we will discuss the pro- and anti-inflammatory functions of these fatty acids and their role in chronic inflammation and cancer progression.

scholarly journals Omega-3 polyunsaturated fatty acids and the inflammatory state of the Caco-2 gut epithelium model

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Luke Durkin ◽  
Caroline Childs ◽  
Philip Calder
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Tight Junction ◽  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Paracellular Permeability ◽  
Omega 3 ◽  
Gut Epithelium ◽  
Anti Inflammatory

AbstractThe gut epithelium is a protective interface between the external environment and the human body. This epithelium interacts with a multitude of internal stimuli from the bloodstream and immune cells, and luminal stimuli from microorganisms and the diet. Disruptions to the epithelium are seen in inflammatory bowel diseases and coeliac disease. The human adenocarcinoma cell line (Caco-2) is an in vitro model used to assess the interactions between nutrients and gut epithelium. Long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory effects via the production of anti-inflammatory eicosanoids, interactions with immune cells and reductions in pro-inflammatory cytokines and chemokines. The aim of this study is to assess the anti-inflammatory properties of DHA and EPA in stimulated Caco-2 monolayers. Caco-2 cells were seeded at 70,000 cells/cm2 and grown to confluence before being allowed to fully differentiate (approx. 21 days total). Cytokines (TNF-α, IFN-γ, and IL-1β) and peptic-tryptic (PT-) gliadin were used as inflammatory stimulants. EPA and DHA incubations occurred 48 hours pre-stimulation. Tight junction function and morphology was determined using trans-epithelial electrical resistance measurements and confocal microscopy. Inflammatory markers, including IL-6, IL-8, and IL-17, were assessed by multiplex. Stimulatory cytokines induced tight junction dysfunction and increased pro-inflammatory mediator production in Caco-2 cells. PT-gliadin, DHA and EPA treatment did not alter paracellular permeability or stimulant-induced production of pro-inflammatory mediators. Further investigation of the inflammatory role of n-3 PUFAs and PT-gliadin in the Caco-2 model is required. Future work will assess the composition of PT-gliadin by electrophoresis and whether co-incubation of n-3 PUFAs and inflammatory cytokines will alter paracellular permeability and mediator output of Caco-2 cells.

scholarly journals Application of Anti-Inflammatory Agents in Prostate Cancer

2020 ◽  
Vol 9 (8) ◽  
pp. 2680
Author(s):  
Koji Hatano ◽  
Kazutoshi Fujita ◽  
Norio Nonomura
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Cancer Development ◽  
Intercellular Signaling ◽  
Inflammatory Microenvironment ◽  
Anti Inflammatory

Chronic inflammation is a major cause of human cancers. The environmental factors, such as microbiome, dietary components, and obesity, provoke chronic inflammation in the prostate, which promotes cancer development and progression. Crosstalk between immune cells and cancer cells enhances the secretion of intercellular signaling molecules, such as cytokines and chemokines, thereby orchestrating the generation of inflammatory microenvironment. Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) play pivotal roles in inflammation-associated cancer by inhibiting effective anti-tumor immunity. Anti-inflammatory agents, such as aspirin, metformin, and statins, have potential application in chemoprevention of prostate cancer. Furthermore, pro-inflammatory immunity-targeted therapies may provide novel strategies to treat patients with cancer. Thus, anti-inflammatory agents are expected to suppress the “vicious cycle” created by immune and cancer cells and inhibit cancer progression. This review has explored the immune cells that facilitate prostate cancer development and progression, with particular focus on the application of anti-inflammatory agents for both chemoprevention and therapeutic approach in prostate cancer.

scholarly journals Metabonomics Reveals Drastic Changes in Anti-Inflammatory/Pro-Resolving Polyunsaturated Fatty Acids-Derived Lipid Mediators in Leprosy Disease

2013 ◽  
Vol 7 (8) ◽  
pp. e2381 ◽  
Author(s):  
Julio J. Amaral ◽  
Luis Caetano M. Antunes ◽  
Cristiana S. de Macedo ◽  
Katherine A. Mattos ◽  
Jun Han ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Lipid Mediators ◽  
Anti Inflammatory

scholarly journals Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769225 ◽  
Author(s):  
Nahla E El-Ashmawy ◽  
Eman G Khedr ◽  
Hoda A El-Bahrawy ◽  
Samar M Al-Tantawy
Keyword(s):  
Fatty Acids ◽  
Bladder Cancer ◽  
Polyunsaturated Fatty Acids ◽  
Molecular Mechanisms ◽  
Combined Treatment ◽  
Lipid Peroxidation Product ◽  
Apoptotic Bodies ◽  
Omega 3 ◽  
Chemopreventive Effect ◽  
Anti Inflammatory

Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as adjuvant therapy with other chemotherapeutics.

scholarly journals Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Austin Ferro ◽  
Yohan S. S. Auguste ◽  
Lucas Cheadle
Keyword(s):  
Brain Development ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Neural Activity ◽  
Signaling Molecules ◽  
Evolutionary Strategy ◽  
Inflammatory Signaling ◽  
Peripheral Tissues ◽  
And Function ◽  
The Brain

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.

scholarly journals Therapeutic Applicability of Anti-Inflammatory and Proresolving Polyunsaturated Fatty Acid-Derived Lipid Mediators

2010 ◽  
Vol 10 ◽  
pp. 676-712 ◽  
Author(s):  
Gerard L. Bannenberg
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Polyunsaturated Fatty Acids ◽  
Host Defense ◽  
Inflammatory Disease ◽  
Lipid Mediators ◽  
Molecular Pathways ◽  
Tissue Protection ◽  
Anti Inflammatory ◽  
Long Chain

The enzymatic oxygenation of polyunsaturated fatty acids by lipoxygenases and cyclo-oxygenases is a resourceful mode of formation of specific autacoids that regulate the extent and pace of the inflammatory response. Arachidonate-derived eicosanoids, such as lipoxin A4, prostaglandin (PG)D2, PGF2α, PGE2, and PGD2-derived cyclopentenones exert specific roles in counter-regulating inflammation and turning on resolution. Recently recognized classes of autacoids derived from long-chain ω-3 polyunsaturated fatty acids, the E- and D-series resolvins, protectin D1, and maresin 1, act as specialized mediators to dampen inflammation actively, afford tissue protection, stimulate host defense, and activate resolution. It is held that counter-regulatory lipid mediators and the specific molecular pathways activated by such endogenous agonists may be suitable for pharmacological use in the treatment of inflammatory disease. The anti-inflammatory drug aspirin is a striking example of a drug that is able to act in such a manner, namely through triggering the formation of 15-epi-lipoxin A4and aspirin-triggered resolvins. Different aspects of the therapeutic applicability of lipid mediators have been addressed here, and indicate that the development of innovative pharmacotherapy based on anti-inflammatory and proresolution lipid mediators presents novel prospects for the treatment of inflammatory disease.

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