Optimization of methods and treatment conditions for studying effects of fatty acids on cell growth

Tronstad, Karl Johan; Berge, Kjetil; Flindt, Esben N.; Kristiansen, Karsten; Berge, Rolf K.

doi:10.1007/s11745-001-0722-8

Cited by 17 publications

(16 citation statements)

References 27 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TSA was given as a complex with BSA, which is acknowledged to reduce the cellular uptake, and hence the toxicity. 32 Propidium iodide staining, followed by flow cytometry, showed a very modest increase in nonviable cells (Ͻ8%) during TSA exposure (data not shown). Although we lack data on IL-4 release in PHA-stimulated cells and on IL-10 release in LPS stimulated cells on lower TSA concentrations, 25 mol/L TSA was also demonstrated to decrease IL-2 release in PHA-stimulated cells and to increase IL-10 release in PHA and TNF-␣ stimulated cells (data not shown).…”

Section: Release Of Cytokines In Pbmcsmentioning

confidence: 90%

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Dyrøy

Røst

Pettersen

et al. 2007

ATVB

View full text Add to dashboard Cite

Objective-Antioxidants protect against oxidative stress and inflammation, which, in combination with hyperlipidemia, are important mediators of atherogenesis. Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid (TSA), which is hypothesized to have antioxidant, antiinflammatory, and hypolipidemic properties. Methods and Results-We show that TSA exerts antioxidant properties by delaying the onset of oxidation of human low density lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages, and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also showed antiinflammatory effects by suppressing the release of interleukin (IL)-2 and -4, and by increasing the release of IL-10 in human blood leukocytes. In addition, TSA decreased the plasma triacylglycerol level and increased the mitochondrial fatty acid ␤-oxidation in rat liver. In pigs, TSA seemed to reduce coronary artery intimal thickening after percutaneous coronary intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner. Conclusions-Our data suggest that TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties, potentially involving PPAR-related mechanisms. Based on these effects, it is tempting to hypothesize that TSA could be an interesting antiatherogenic approach to atherosclerotic disorders. A therosclerosis is regarded as an inflammatory disorder of the vascular wall, where multiple factors contribute to a persistent and self-perpetual inflammation within the atherosclerotic lesions. [1][2][3][4][5] There is also a consensus that atherosclerosis represents a state of elevated oxidative stress characterized by lipid and protein oxidation in the vascular wall. 6 Enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders.We have previously shown that tetradecylthioacetic acid (TTA), a modified fatty acid with a sulfur atom in the third position of the carbon backbone, promotes mitochondrial and peroxisomal proliferation, and decreases serum lipid levels in animal models. 7-9 TTA also shows antioxidant effects in vitro 10 and encompasses antiinflammatory properties in human leukocytes. 11 The pleiotropic effects of TTA seem to involve activation of peroxisome proliferator-activated receptors (PPARs), 12,13 which are receptors that serves as an important link between lipid metabolism and inflammation. 14 -17 Tetradecylselenoacetic acid (TSA) is a novel fatty acid which in comparison to TTA has a selenium atom instead of a sulfur atom in third position of the carbon backbone. As with TTA, 18 this modification makes TSA resistant to fatty acid ␤-oxidation. A previous in vitro study has demonstrated that TSA is a stronger antioxidant than TTA. 19 Based on these findings and its relation to TTA, we hypothesized that TSA also exerts poten...

show abstract

Section: Release Of Cytokines In Pbmcsmentioning

confidence: 90%

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Dyrøy

Røst

Pettersen

et al. 2007

ATVB

View full text Add to dashboard Cite

show abstract

“…The cells were allowed to settle overnight before the treatments were started. Fatty acid solutions were prepared as described earlier (25).…”

Section: Cell Culturesmentioning

confidence: 99%

“…This might be related to their capacity to modulate mitochondrial oxidation and thereby lipid accumulation. Therefore, D54Mg cells were incubated with 150 M TTA or PA, which are reported to be the approximate IC 50 concentration of TTA after 48 h of cultivation (25), in the presence of l -carnitine and inhibitors of mitochondrial fatty acid oxidation. l -carnitine, which is essential for mitochondrial transmembrane transport [reviewed in ref.…”

Section: Relation Between Fatty Acid Oxidation and Cell Growthmentioning

confidence: 99%

Impact of mitochondrial β-oxidation in fatty acid-mediated inhibition of glioma cell proliferation

Berge

Tronstad

Bohov

et al. 2003

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Tetradecylthioacetic acid (TTA), which cannot be ␤ -oxidized, exerts growth-limiting properties in glioma cells. In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatty acid palmitic acid (PA), in the presence of l -carnitine and the carnitine palmitoyltransferase inhibitors etomoxir and aminocarnitine. l -carnitine partly abolished the PA-mediated growth reduction of glioma cells, whereas etomoxir and aminocarnitine enhanced the antiproliferative effect of PA. The production of acid-soluble products increased and the incorporation of PA into glycerolipids decreased after l -carnitine supplementation. l -carnitine was found to enhance the antiproliferative effect of TTA, but did not affect the incorporation of TTA into glycerolipids, or ceramide. PDMP, sphingosine 1-phosphate, desipramine, fumonisin B 1 , and l -cycloserine were able not to rescue the glioma cells from PA and TTAinduced growth inhibition, suggesting that increased ceramide production is not important in the growth reduction. TTAmediated growth inhibition was accompanied with an increased uptake of PA and increased incorporation of PA into triacylglycerol (TG). Our data suggest that mitochondrial functions are involved in fatty acid-mediated growth inhibition. Whether there is a causal relationship between TG accumulation and the apoptotic process remains to be determined.-Berge, K., K. J. Tronstad, P. Bohov, L. Madsen, and R. K. Berge. Impact of mitochondrial ␤ -oxidation in fatty acid-mediated inhibition of glioma cell proliferation.

show abstract

“…TTA and PA were complexed to BSA as described previously. 25 The culture medium consisted of RPMI 1640 with glutamine and Hepes (Gibco, Paisley, UK) supplemented with gentamicin 100 g/ml and 10% fetal calf serum (FCS; HyClone, Leukemia Logan, UT, USA). Recombinant human cytokines were used at the following concentrations: 50 ng/ml granulocyte-macrophage colony-stimulating factor (GM-CSF; Sandoz, Basel, Switzerland), 50 ng/ml interleukin-3 (IL-3; PeproTech EC, London, UK), 50 ng/ml stem cell factor (SCF; PeproTech), 50 ng/ml Flt3-ligand (Flt3-L; R&D Systems, Abingdon, UK), and 50 ng/ml interleukin-2 (IL-2; PeproTech).…”

Section: Chemicalsmentioning

confidence: 99%

“…Administration of TTA to cell cultures has demonstrated that this 3-thia fatty acid inhibits proliferation of malignant cells from various origins. 16,[24][25][26][27] The mechanisms behind the antiproliferative effects of TTA are still elusive.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative effects of a non-β-oxidizable fatty acid, tetradecylthioacetic acid, in native human acute myelogenous leukemia blast cultures

et al. 2002

View full text Add to dashboard Cite

The lipid metabolism is important in the regulation of cell proliferation. We have examined effects of a fatty acid analogue, tetradecylthioacetic acid (TTA), on the functional phenotype of native, human AML cells. TTA inhibited AML blast proliferation in the presence of single cytokines (GM-CSF and SCF: P Ͼ 0.05, 35 patients with detectable proliferation) and a combination of cytokines (P Ͻ 0.005, n = 21). This antiproliferative effect was generally stronger than for the normal fatty acid palmitic acid (PA). Both TTA and PA increased the secretion of tumor necrosis factor ␣ (TNF␣) (P Ͻ 0.05, 27 patients with detectable cytokine release), but only PA increased interleukein 1␤ (IL-1␤) release (P Ͻ 0.005, n = 34). AML blast populations varied significantly in their levels and activities of metabolites and enzymes characterizing oxidative status and fatty acid metabolism, and there was no significant correlation between the intrinsic oxidative status and the effects of PA and TTA on blast proliferation. Although TTA reduced the proliferation of mitogen-stimulated normal T cells derived from healthy individuals (P Ͻ 0.05, n = 8), no adverse effects were seen on peripheral blood cell counts (reticulocytes, platelets, total white blood cells, differential leukocyte counts) for healthy volunteers receiving TTA (oral administration of 1000 mg/day for 7 consecutive days). Our results suggest that TTA can inhibit AML blast proliferation through pathways that are unrelated to autocrine cytokine secretion and intrinsic oxidative status.

show abstract

Optimization of methods and treatment conditions for studying effects of fatty acids on cell growth

Cited by 17 publications

References 27 publications

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Impact of mitochondrial β-oxidation in fatty acid-mediated inhibition of glioma cell proliferation

Antiproliferative effects of a non-β-oxidizable fatty acid, tetradecylthioacetic acid, in native human acute myelogenous leukemia blast cultures

Contact Info

Product

Resources

About