scholarly journals Effect of Dietaryω-3 Polyunsaturated Fatty Acid DHA on Glycolytic Enzymes and Warburg Phenotypes in Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Laura Manzi ◽  
Lara Costantini ◽  
Romina Molinari ◽  
Nicolò Merendino

The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are a class of lipids that has been shown to have beneficial effects on some chronic degenerative diseases such as cardiovascular diseases, rheumatoid arthritis, inflammatory disorders, diabetes, and cancer. Amongω-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) has received particular attention for its antiproliferative, proapoptotic, antiangiogenetic, anti-invasion, and antimetastatic properties, even though the involved molecular mechanisms are not well understood. Recently, somein vitrostudies showed that DHA promotes the inhibition of glycolytic enzymes and the Warburg phenotype. For example, it was shown that in breast cancer cell lines the modulation of bioenergetic functions is due to the capacity of DHA to activate the AMPK signalling and negatively regulate the HIF-1αfunctions. Taking into account these considerations, this review is focused on current knowledge concerning the role of DHA in interfering with cancer cell metabolism; this could be considered a further mechanism by which DHA inhibits cancer cell survival and progression.

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

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.


Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2306
Author(s):  
Simona Serini ◽  
Gabriella Calviello

Long-chain Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are widely recognized as powerful negative regulators of acute inflammation. However, the precise role exerted by these dietary compounds during the healing process is still largely unknown, and there is increasing interest in understanding their specific effects on the implicated cells/molecular factors. Particular attention is being focused also on their potential clinical application in chronic pathologies characterized by delayed and impaired healing, such as diabetes and vascular diseases in lower limbs. On these bases, we firstly summarized the current knowledge on wound healing (WH) in skin, both in normal conditions and in the setting of these two pathologies, with particular attention to the cellular and molecular mechanisms involved. Then, we critically reviewed the outcomes of recent research papers investigating the activity exerted by Omega-3 PUFAs and their bioactive metabolites in the regulation of WH in patients with diabetes or venous insufficiency and showing chronic recalcitrant ulcers. We especially focused on recent studies investigating the mechanisms through which these compounds may act. Considerations on the optimal dietary doses are also reported, and, finally, possible future perspectives in this area are suggested.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
S. C. Sargi ◽  
M. M. O. Dalalio ◽  
A. G. Moraes ◽  
J. E. L. Visentainer ◽  
D. R. Morais ◽  
...  

There has recently been increased interest in the potential health effects of omega-3 polyunsaturated fatty acids on the immune system. Paracoccidioidomycosis is the most important endemic mycosis in Latin America. Macrophages have a fundamental role and act as first line of organism defense. The purpose of this study was to analyze the effect of n-3 fatty acids on the production of PGE2and NO by mice infected with Pb18 and fed a diet enriched with LNA for 8 weeks. To study the effect of omega-3 fatty acids on macrophage activity during experimental paracoccidioidomycosis, mice were infected with Pb18 and fed a diet supplemented with LNA. PGE2in the serum of animals was analyzed and NO in the supernatants of macrophages cultured and challengedin vitrowith Pb18 was measured. Omega-3 fatty acids seemed to decrease the production of PGE2in vivoin the infected group fed an LNA-supplemented diet during the 4th and 8th weeks of the experiment. At the same time, we observed an increase in synthesis of NO by peritoneal macrophages in this group. Omega-3 fatty acids thus appear to have an immunomodulatory effect in paracoccidioidomycosis.


2019 ◽  
Vol 27 (1) ◽  
pp. 47-63
Author(s):  
Farheen Jameel ◽  
Priyanka Agarwal ◽  
Mohd. Arshad ◽  
Mohd. Serajuddin

Abstract Fish are a major dietary source of n-3 and n-6 polyunsaturated fatty acids (PUFAs) in humans since the human body lacks the necessary enzymes required to synthesize them. Diets rich in fish oil containing n-3 fatty acids have been shown to lower the incidence rates of cancer. They have also been shown to have cytotoxic or anti-proliferative effects on a variety of human cancer cell lines, and they are known to nurture overall human health without any observable side effects. The present review focused on in-vitro research findings regarding the apoptotic and anti-proliferative role of n-3 fatty acids FAs that highlight the important mechanisms and pathways of their action in inhibiting the progression of cancer. A survey of the literature indicated the paucity of information on the use of n-3 FAs in combination with other anticancer substances. Therefore, further research needs to be undertaken on the use of n-3 FAs in combination with other anticancer phytochemicals and drugs, the use of antibodies as specific carriers of n-3 FAs, and different increasing ratios of n-3/n-6 FAs that not only control the side effects of chemotherapy but also enhance its efficacy and selectivity. These FAs might also prove to be a pioneer therapy against cancer.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Luke Durkin ◽  
Caroline Childs ◽  
Philip Calder

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.


Author(s):  
Jaya Sriram ◽  
Olorunfemi Adetona ◽  
Tonya Orchard ◽  
Chieh-Ming Wu ◽  
James Odei

Airborne particulate matter (PM) exposure remains the leading environmental risk factor for disease globally. Interventions to mitigate the adverse effects of PM are required, since there is no discernible threshold for its effects, and exposure reduction approaches are limited. The mitigation of PM (specifically diesel exhaust particles (DEP))-induced release of pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) and vasoconstrictor endothelin-1 (ET-1) after 24 and 48 h of exposure by pre-treatment with individual pure, combined pure, and an oil formulation of two fish oil omega-3 polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were all tested at an equivalent concentration of 100 µM in vitro in human umbilical vein endothelial cells. The PUFAs and fish oil formulation completely mitigated or diminished the DEP-induced release of IL-6, IL-8, and ET-1 by 14–78%. DHA was more effective in reducing the levels of the DEP-induced release of the cytokines, especially IL-6 after 48 h of DEP exposure in comparison to EPA (p < 0.05), whereas EPA seemed to be more potent in reducing ET-1 levels. The potential of fish ω-3 PUFAs to mitigate PM-induced inflammation and vasoactivity was demonstrated by this study.


Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 639 ◽  
Author(s):  
Younghyun Lim ◽  
Seyoung Kim ◽  
Sehoon Kim ◽  
Dong-In Kim ◽  
Kyung Won Kang ◽  
...  

The immune-suppressive effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whether n-3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. The expansion of anti-viral CD8+ T cells that endogenously synthesize n-3 PUFAs (FAT-1) dramatically decreased upon lymphocytic choriomeningitis virus (LCMV) infection in vivo. This decrease was not caused by the considerable reduction of TCR expression or the impaired chemotactic activity of T cells. Interestingly, a highly inclined and laminated optical sheet (HILO) microscopic analysis revealed that the TCR motility was notably reduced on the surface of the FAT-1 CD8+ T cells compared to the wild type (WT) CD8+ T cells. Importantly, the adhesion strength of the FAT-1 CD8+ T cells to the peptide-MHC was significantly lower than that of the WT CD8+T cells. Consistent with this result, treatment with docosahexaenoic acid (DHA), one type of n-3 PUFA, significantly decreased CD8+ T cell adhesion to the pMHC. Collectively, our results reveal a novel mechanism through which n-3 PUFAs decrease TCR-pMHC interactions by modulating TCR mobility on CD8+ T cell surfaces.


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