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.

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 Activation of Peroxisome Proliferator-activated Receptor α (PPARα) Suppresses Hypoxia-inducible Factor-1α (HIF-1α) Signaling in Cancer Cells

2012 ◽  
Vol 287 (42) ◽  
pp. 35161-35169 ◽  
Author(s):  
Jundong Zhou ◽  
Shuyu Zhang ◽  
Jing Xue ◽  
Jori Avery ◽  
Jinchang Wu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Proteasome Inhibitors ◽  
Tube Formation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Properties ◽  
Pparγ Agonist ◽  
Expression And Activity

Activation of peroxisome proliferator-activated receptor α (PPARα) has been demonstrated to inhibit tumor growth and angiogenesis, yet the mechanisms behind these actions remain to be characterized. In this study, we examined the effects of PPARα activation on the hypoxia-inducible factor-1α (HIF-1α) signaling pathway in human breast (MCF-7) and ovarian (A2780) cancer cells under hypoxia. Incubation of cancer cells under 1% oxygen for 16 h significantly induced HIF-1α expression and activity as assayed by Western blotting and reporter gene analysis. Treatment of the cells with PPARα agonists, but not a PPARγ agonist, prior to hypoxia diminished hypoxia-induced HIF-1α expression and activity, and addition of a PPARα antagonist attenuated the suppression of HIF-1α signaling. Activation of PPARα attenuated hypoxia-induced HA-tagged HIF-1α protein expression without affecting the HA-tagged HIF-1α mutant protein level, indicating that PPARα activation promotes HIF-1α degradation in these cells. This was further confirmed using proteasome inhibitors, which reversed PPARα-mediated suppression of HIF-1α expression under hypoxia. Using the co-immunoprecipitation technique, we found that activation of PPARα enhances the binding of HIF-1α to von Hippel-Lindau tumor suppressor (pVHL), a protein known to mediate HIF-1α degradation through the ubiquitin-proteasome pathway. Following PPARα-mediated suppression of HIF-1α signaling, VEGF secretion from the cancer cells was significantly reduced, and tube formation by endothelial cells was dramatically impaired. Taken together, these findings demonstrate for the first time that activation of PPARα suppresses hypoxia-induced HIF-1α signaling in cancer cells, providing novel insight into the anticancer properties of PPARα agonists.

scholarly journals [Corrigendum] A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

2020 ◽  
Author(s):  
Alejandro Schcolnik‑Cabrera ◽  
Guadalupe Dominguez‑G�mez ◽  
Alma Ch�vez‑Blanco ◽  
Marisol Ram�rez‑Yautentzi ◽  
Roc�o Morales‑B�rcenas ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Human Colon ◽  
Acid Synthesis ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

scholarly journals Role of peroxisome proliferator-activated receptor-α on the synthesis of monounsaturated fatty acids in goat mammary epithelial cells

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Huibin Tian ◽  
Jun Luo ◽  
Hengbo Shi ◽  
Xiaoying Chen ◽  
Jiao Wu ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Mammary Epithelial Cells ◽  
Acid Synthesis ◽  
Mammary Epithelial ◽  
Mrna Abundance ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Goat Mammary Epithelial Cells

Abstract A key member of the nuclear receptor superfamily is the peroxisome proliferator-activated receptor alpha (PPARA) isoform, which in nonruminants is closely associated with fatty acid oxidation. Whether PPARA plays a role in milk fatty acid synthesis in ruminants is unknown. The main objective of the present study was to use primary goat mammary epithelial cells (GMEC) to activate PPARA via the agonist WY-14643 (WY) or to silence it via transfection of small-interfering RNA (siRNA). Three copies of the peroxisome proliferator-activated receptor response element (PPRE) contained in a luciferase reporter vector were transfected into GMEC followed by incubation with WY at 0, 10, 20, 30, 50, or 100 µM. A dose of 50 µM WY was most effective at activating PPRE without influencing PPARA mRNA abundance. Transfecting siRNA targeting PPARA decreased its mRNA abundance to 20% and protein level to 50% of basal levels. Use of WY upregulated FASN, SCD1, ACSL1, DGAT1, FABP4, and CD36 (1.1-, 1.5-, 2-, 1.4-, 1.5-, and 5-fold, respectively), but downregulated DGAT2 and PGC1A (−20% and −40%, respectively) abundance. In contrast, triacylglycerol concentration decreased and the content and desaturation index of C16:1 and C18:1 increased. Thus, activation of PPARA via WY appeared to channel fatty acids away from esterification. Knockdown of PPARA via siRNA downregulated ACACA, SCD1, AGPAT6, CD36, HSL, and SREBF1 (−43%, −67%, −16%, −56%, −26%, and −29%, respectively), but upregulated ACSL1, DGAT2, FABP3, and PGC1A (2-, 1.4-, 1.3-, and 2.5-fold, respectively) mRNA abundance. A decrease in the content and desaturation index of C16:1 and C18:1 coupled with an increase in triacylglycerol content accompanied those effects at the mRNA level. Overall, data suggest that PPARA could promote the synthesis of MUFA in GMEC through its effects on mRNA abundance of genes related to fatty acid synthesis, oxidation, transport, and triacylglycerol synthesis.

Mushroom small RNAs as potential anticancer agents: a closer look at Cantharellus cibarius proapoptotic and antiproliferative effects in colon cancer cells

2019 ◽  
Vol 10 (5) ◽  
pp. 2739-2751 ◽  
Author(s):  
Marta K. Lemieszek ◽  
Patrícia S. Marques ◽  
Miguel Ribeiro ◽  
Daniela Ferreira ◽  
Guilhermina Marques ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Small Rnas ◽  
Colon Cancer Cells ◽  
Antiproliferative Effects ◽  
Anticancer Properties

Screening aimed at the evaluation of the presence of small RNAs with anticancer properties in Boletus spretus, B. pinophilus and Cantharellus cibarius, was conducted.

scholarly journals Peroxisome-proliferator-activated receptor δ mediates the effects of long-chain fatty acids on post-confluent cell proliferation

2000 ◽  
Vol 350 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Chantal JEHL-PIETRI ◽  
Claire BASTIE ◽  
Isabelle GILLOT ◽  
Serge LUQUET ◽  
Paul A. GRIMALDI
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Ectopic Expression ◽  
Peroxisome Proliferator ◽  
Long Chain Fatty Acids ◽  
Control Of Gene Expression ◽  
Long Chain ◽  
Chain Fatty Acids

Nutritional long-chain fatty acids control adipose tissue mass by regulating the number and the size of adipocytes. It is now established that peroxisome-proliferator-activated receptors (PPARs) play crucial functions in the control of gene expression and the level of cell differentiation. PPARγ, which is activated by specific prostanoids, is a key factor in activating terminal differentiation and adipogenesis. We have recently demonstrated that PPARδ, once activated by fatty acids, drives the expression of a limited set of genes, including that encoding PPARγ, thereby inducing adipose differentiation. Thus far, the mechanism of action of fatty acids in the control of preadipocyte proliferation has remained unknown. We show here that PPARδ is directly implicated in fatty acid-induced cell proliferation. Ectopic expression of PPARδ renders 3T3C2 cells capable of responding to treatment with long-chain fatty acids by a resumption of mitosis, and this effect is limited to a few days after confluence. This response is restricted to PPARδ activators and, for fatty acids, takes place within the range of concentrations found to trigger differentiation of preadipocytes both in vitro and in vivo. Furthermore, the use of a mutated inactive PPARδ demonstrated that transcriptional activity of the nuclear receptor is required to mediate fatty acid-induced proliferation. These data demonstrate that PPARδ, as a transcription factor, is directly implicated in fatty acid-induced proliferation, and this could explain the hyperplastic development of adipose tissue that occurs in high-fat-fed animals.

scholarly journals Peroxisome proliferator-activated receptor ligands regulate lipid content, metabolism, and composition in fetal lungs of diabetic rats

2014 ◽  
Vol 220 (3) ◽  
pp. 345-359 ◽  
Author(s):  
M Kurtz ◽  
E Capobianco ◽  
V Careaga ◽  
N Martinez ◽  
M B Mazzucco ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Olive Oil ◽  
Lung Development ◽  
Maternal Diabetes ◽  
Diabetic Rats ◽  
Lipid Homeostasis ◽  
Safflower Oil ◽  
Peroxisome Proliferator ◽  
Fetal Lungs ◽  
Ppar Ligands

Maternal diabetes impairs fetal lung development. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors relevant in lipid homeostasis and lung development. This study aims to evaluate the effect ofin vivoactivation of PPARs on lipid homeostasis in fetal lungs of diabetic rats. To this end, we studied lipid concentrations, expression of lipid metabolizing enzymes and fatty acid composition in fetal lungs of control and diabetic rats i) after injections of the fetuses with Leukotriene B4(LTB4, PPARα ligand) or 15deoxyΔ12,14prostaglandin J2(15dPGJ2, PPARγ ligand) and ii) fed during pregnancy with 6% olive oil- or 6% safflower oil-supplemented diets, enriched with PPAR ligands were studied. Maternal diabetes increased triglyceride concentrations and decreased expression of lipid-oxidizing enzymes in fetal lungs of diabetic rats, an expression further decreased by LTB4and partially restored by 15dPGJ2in lungs of male fetuses in the diabetic group. In lungs of female fetuses in the diabetic group, maternal diets enriched with olive oil increased triglyceride concentrations and fatty acid synthase expression, while those enriched with safflower oil increased triglyceride concentrations and fatty acid transporter expression. Both olive oil- and safflower oil-supplemented diets decreased cholesterol and cholesteryl ester concentrations and increased the expression of the reverse cholesterol transporter ATP-binding cassette A1 in fetal lungs of female fetuses of diabetic rats. In fetal lungs of control and diabetic rats, the proportion of polyunsaturated fatty acids increased with the maternal diets enriched with olive and safflower oils. Our results revealed important changes in lipid metabolism in fetal lungs of diabetic rats, and in the ability of PPAR ligands to modulate the composition of lipid species relevant in the lung during the perinatal period.

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