scholarly journals Omega-3 Fatty Acids and PPARγin Cancer

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Iris J. Edwards ◽  
Joseph T. O'Flaherty
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Dietary Fatty Acids ◽  
Human Populations ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
New Paradigm

Omega-3 (or n-3) polyunsaturated fatty acids (PUFAs) and their metabolites are natural ligands for peroxisome proliferator receptor activator (PPAR)γand, due to the effects of PPARγon cell proliferation, survival, and differentiation, are potential anticancer agents. Dietary intake of omega-3 PUFAs has been associated with a reduced risk of certain cancers in human populations and in animal models. In vitro studies have shown that omega-3 PUFAs inhibit cell proliferation and induce apoptosis in cancer cells through various pathways but one of which involves PPARγactivation. The differential activation of PPARγand PPARγ-regulated genes by specific dietary fatty acids may be central to their distinct roles in cancer. This review summarizes studies relating PUFAs to PPARγand cancer and offers a new paradigm relating an n-3 PUFA through PPARγto the expression of the cell surface proteoglycan, syndecan-1, and to the death of cancer cells.

scholarly journals Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids increase inflammation in primary lung mesenchymal cells

2018 ◽  
Vol 314 (6) ◽  
pp. L922-L935 ◽  
Author(s):  
Sandra Rutting ◽  
Dia Xenaki ◽  
Edmund Lau ◽  
Jay Horvat ◽  
Lisa G. Wood ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Epithelial Cells ◽  
Airway Inflammation ◽  
Saturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Obese Person ◽  
Tnf Α ◽  
Phosphoinositide 3 Kinase

Obesity is an important risk factor for developing severe asthma. Dietary fatty acids, which are increased in sera of obese individuals and after high-fat meals, activate the innate immune system and induce inflammation. This study investigated whether dietary fatty acids directly cause inflammation and/or synergize with obesity-induced cytokines in primary human pulmonary fibroblasts in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [ω-6 polyunsaturated fatty acids (PUFAs) and ω-3 PUFAs or saturated fatty acids (SFAs)], with or without TNF-α, and release of the proinflammatory cytokines, IL-6 and CXCL8, was measured. We found that the ω-6 PUFA arachidonic acid (AA), but not ω-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined AA and TNF-α challenge resulted in substantially greater cytokine release than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK reduced CXCL8 release, induced by AA and TNF-α alone, but not in combination. Synergistic CXCL8 release, following AA and TNF-α challenge, was not medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase, and NF-κB) nor by hyperactivation of NF-κB or p38. To investigate if these findings occur in other airway cells, effects of AA in primary human airway smooth muscle (ASM) cells and human bronchial epithelial cells were also investigated. We found proinflammatory effects in ASM cells but not epithelial cells. This study suggests that diets rich in ω-6 PUFAs might promote airway inflammation via multiple pathways, including COX-dependent and -independent pathways, and in an obese person, may lead to more severe airway inflammation.

Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPARα

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1340-1346 ◽  
Author(s):  
Sanjeev Sethi ◽  
Ouliana Ziouzenkova ◽  
Heyu Ni ◽  
Denisa D. Wagner ◽  
Jorge Plutzky ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fish Oil ◽  
Inflammatory Diseases ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Peroxisome Proliferator Activated Receptor

Omega-3 fatty acids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor α (PPARα), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)–treated mice. This occurred via a PPARα-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPARα-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPARα-mediated anti-inflammatory effect of oxidized EPA.

scholarly journals Mobilization efficiency is critically regulated by fat via marrow PPARδ

Haematologica ◽  
2021 ◽  
Author(s):  
Tomohide Suzuki ◽  
Shinichi Ishii ◽  
Masakazu Shinohara ◽  
Yuko Kawano ◽  
Kanako Wakahashi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mrna Level ◽  
Normal Diet ◽  
Dietary Fatty Acids ◽  
Lipid Mediator ◽  
Peroxisome Proliferator ◽  
Strong Positive Correlation ◽  
Hematopoietic Stem

The mobilization efficiency of hematopoietic stem/progenitor cells from bone marrow (BM) to circulation by granulocyte colony-stimulating factor (G-CSF) is dramatically dispersed in humans and mice with no mechanistic lead for poor mobilizers. The regulatory mechanism for mobilization efficiency by dietary fat was assessed in mice. Fat-free diet (FFD) for 2 weeks greatly increased mobilization compared to normal diet (ND). The BM mRNA level of peroxisome proliferator-activated receptor δ (PPARδ), a receptor for lipid mediators, was markedly up-regulated by G-CSF in mice fed with ND and displayed strong positive correlation with widely scattered mobilization efficiency. It was hypothesized that BM fat ligand for PPARδ might inhibit mobilization. The PPARδ agonist inhibited mobilization in mice fed with ND and enhanced mobilization by FFD. Treatment with the PPARδ antagonist and chimeric mice with PPARδ+/- BM showed enhanced mobilization. Immunohistochemical staining and flow cytometry revealed that BM PPARδ expression was enhanced by G-CSF mainly in mature/immature neutrophils. BM lipid mediator analysis revealed that G-CSF treatment and FFD resulted in the exhaustion of ω3-polyunsaturated fatty acids such as eicosapentaenoic acid (EPA). EPA induced the up-regulation of genes downstream of PPARδ, such as carnitine palmitoyltransferase-1α and angiopoietin-like protein 4 (Angptl4), in mature/immature neutrophils in vitro and inhibited enhanced mobilization in mice fed with FFD in vivo. Treatment of wild-type mice with the anti-Angptl4 antibody enhanced mobilization together with BM vascular permeability. Collectively, PPARδ signaling in BM mature/immature neutrophils induced by dietary fatty acids negatively regulates mobilization, at least partially, via Angptl4 production.

scholarly journals Anticancer Properties of PPARα-Effects on Cellular Metabolism and Inflammation

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Maja Grabacka ◽  
Krzysztof Reiss
Keyword(s):  
Cell Proliferation ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Basic Research ◽  
Acid Synthesis ◽  
Modern Medicine ◽  
Peroxisome Proliferator ◽  
Anticancer Properties ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors (PPARs) have lately attracted much attention as therapeutic targets. Previously, PPAR ligands were associated with the treatment of diabetes, hyperlipidemia and cardiovascular diseases, as they modulate the expression of genes regulating glucose and lipid metabolism. Recently, PPAR ligands have been also considered as potential anticancer agents, with relatively low systemic toxicity. The emerging evidence for antiproliferative, proapoptotic, antiinflammatory and potential antimetastatic properties of PPARαligands prompted us to discuss possible roles of PPARαin tumor suppression. PPARαactivation can target cancer cells energy balance by blocking fatty acid synthesis and by promoting fatty acidβ-oxidation. In the state of limited nutrient availability, frequently presents in the tumor microenvironment, PPARαcooperates with AMP-dependent protein kinase in: (i) repressing oncogenic Akt activity, (ii) inhibiting cell proliferation, and (iii) forcing glycolysis-dependent cancer cells into “metabolic catastrophe.” Other potential anticancer effects of PPARαinclude suppression of inflammation, and upregulation of uncoupling proteins (UCPs), which attenuates mitochondrial reactive oxygen species production and cell proliferation. In conclusion, there are strong premises that the low-toxic and well-tolerated PPAR ligands should be considered as new therapeutic agents to fight disseminating cancer, which represents the major challenge for modern medicine and basic research.

Dietary supplementation with omega-3 polyunsaturated fatty acids ameliorates acute pneumonia induced byKlebsiella pneumoniaein BALB/c mice

2013 ◽  
Vol 59 (7) ◽  
pp. 503-510 ◽  
Author(s):  
Sonica Sharma ◽  
Sanjay Chhibber ◽  
Harsh Mohan ◽  
Saroj Sharma
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Interleukin 1 ◽  
Bacterial Load ◽  
Dietary Fatty Acids ◽  
Omega 3 ◽  
Necrosis Factor Alpha ◽  
Pufa Supplementation ◽  
Acute Pneumonia

The immune benefits associated with the optimal intake of dietary fatty acids are widely known. The objective of the present investigation was to elucidate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) food source on acute pneumonia induced by Klebsiella pneumoniae. Three different n-3 PUFA preparations (cod liver oil, Maxigard, and flaxseed oil) were orally supplemented and infection was induced in different groups of experimental mice. Mice fed olive oil and normal saline served as oil and saline controls, respectively. After 2 weeks of fatty acid feeding, no effect on the establishment of infection was observed when acute pneumonia was induced in animals. On the other hand, 6 weeks of n-3 PUFA administration was found to improve resistance in mice, as reduced lung bacterial load coupled with significant improvement in pathology was seen in infected mice. Alveolar macrophages collected from all 3 groups of mice fed n-3 PUFA exhibited a significant decrease in the level of apoptosis following infection with K. pneumoniae and an enhanced in vitro phagocytic potential for the pathogen. Lower lung levels of nitric oxide, malondialdehyde, and lactate dehydrogenase were associated with a decrease in the severity of tissue damage. There was a significant increase in the lung levels of pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)). No significant change was observed in the levels of interleukin-10 (IL-10). This study highlights that dietary n-3 PUFA supplementation exerts an overall beneficial effect against acute experimental pneumonia. This mechanism is operative through upregulation of nonspecific and specific immune defenses of the host.

Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies

2020 ◽  
Vol 10 (5) ◽  
pp. 577-590
Author(s):  
Jai B. Sharma ◽  
Shailendra Bhatt ◽  
Asmita Sharma ◽  
Manish Kumar
Keyword(s):  
Cancer Cells ◽  
Cellular Uptake ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
In Vitro Cytotoxicity ◽  
Curcumin Nanoparticles ◽  
Cytotoxicity Studies ◽  
Delivery Technique ◽  
Different Types

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.

Sign in / Sign up

Export Citation Format

Share Document