Disease relevance of Lopac-T-1698

• In cultured rat hepatoma and primary hepatocyte cells, fatty acids and the sulfur-substituted fatty acid analog, tetradecylthioacetic acid, robustly induce LXR alpha (up to 3.5- and 7-fold, respectively) but not LXR beta (also called OR-1) mRNA steady state levels, with unsaturated fatty acids being more effective than saturated fatty acids [1].
• TTA represents a modified fatty acid that exerts unique effects on malignant hematopoietic cells, and the present study indicates that TTA may have a therapeutic potential in patients with acute leukemias [2].
• Only TTA inhibited (P < 0.05) leukemic infiltration in the bone marrow and spleen, probably due to apoptosis of the leukemic cells [2].
• EXPERIMENTAL DESIGN: We now examined the effects of PUFA and TTA in rats transplanted with either acute promyelocytic leukemia or acute T-cell leukemia [2].
• PURPOSE: Polyunsaturated fatty acids (PUFA) and the sulfur-substituted fatty acid tetradecylthioacetic acid (TTA) inhibit proliferation and induce apoptosis in lymphoma and leukemic cell lines, but it is unknown if they can modify leukemogenesis in the intact organism [2].

High impact information on Lopac-T-1698

• In contrast, circumstantial evidences suggest that peroxisome proliferator-activated receptor-independent metabolic pathways may be of importance for the antioxidant, antiproliferative and antiinflammatory action of tetradecylthioacetic acid [3].
• As a pan-peroxisome proliferator-activated receptor ligand, tetradecylthioacetic acid regulates the adipose tissue mass and the expression of lipid metabolizing enzymes, particularly those involved in catabolic pathways [3].
• Transient transfections showed a 3.4-, 2.3-, and 2.2-fold induction of C-ACS promoter activity after fenofibric acid, alpha-bromopalmitate, and tetradecylthioacetic acid, respectively [4].
• Therefore, we investigated the mitochondrial contribution in cell death induced by a modified fatty acid, tetradecylthioacetic acid (TTA), which cannot be beta-oxidized [5].
• Tetradecylthioacetic acid and tetradecylselenoacetic acid inhibit lipid peroxidation and interact with superoxide radical [6].

Chemical compound and disease context of Lopac-T-1698

• The 3-thia fatty acid tetradecylthioacetic acid (TTA) has recently been shown to inhibit growth rate and increase peroxisomal acyl-CoA oxidase (ACO) (EC 1.3.99.3) activity in the Morris 7800 C1 hepatoma cells [7].
• We examined the effects of different fatty acids (myristic-, stearic-, linolenic-, oleic-, arachidonic- and tetradecylthioacetic acid (TTA)) and the synthetic glucocorticoid dexamethasone on RXR alpha mRNA and protein steady-state levels in hepatoma cells and cultured hepatocytes [8].
• The objective of the present work was to optimize methods and treatment conditions used for studying antiproliferative effects of fatty acids and analogs, represented by palmitic acid (PA) and the beta-oxidation-restricted fatty acid analog tetradecylthioacetic acid (TTA), in rat (BT4Cn) and human (D54Mg and GaMg) glioma cell lines [9].
• The effects of tetradecylthioacetic acid (TTA), insulin and dexamethasone on palmitoyl-CoA synthetase activity and its mRNA both in 7800 C1 hepatoma cells and cultured rat hepatocytes were studied [10].
• OBJECTIVES: The purpose of this pilot study is to explore the clinical efficacy of the topical application of potent PPARbeta/delta and gamma agonists on plaque psoriasis, tetradecylthioacetic acid (TTA) and rosiglitazone, respectively [11].

Biological context of Lopac-T-1698

• The biological responses to tetradecylthioacetic acid include mitochondrial proliferation, increased catabolism of fatty acids, antiadiposity, improvement in insulin sensitivity, antioxidant properties, reduced proliferation and induction of apoptosis in rapidly proliferating cells, cell differentiation and antiinflammatory action [3].
• 12-O-tetradecanoyl phorbol-13-acetate (TPA), platelet-derived growth factor (PDGF)-BB, or PDGF-AA stimulation of 1-(carboxymethylthio)tetradecane-treated cells resulted in decreased maximal levels of c-fos mRNA expression, indicating attenuation of signal transduction [12].
• Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARalpha activation [13].
• We have examined effects of a fatty acid analogue, tetradecylthioacetic acid (TTA), on the functional phenotype of native, human AML cells [14].
• Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis [15].

Anatomical context of Lopac-T-1698

• These results indicate that culturing the cells with 1-(carboxymethylthio)tetradecane causes looser packing and an increase in fluidity of the diacylphosphatidylethanolamine molecules in the membranes [12].
• Our data demonstrate that 1-(carboxymethylthio)tetradecane-mediated changes in phospholipid structure and composition may affect PDGF- and TPA-mediated c-fos gene regulation in fibroblasts [12].
• Based on these findings, we therefore suggest that tetradecylthioacetic acid mainly affects secretion of lipoproteins in CaCo-2 cells [16].
• Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid [17].
• This was accompanied by a greater volume fraction of mitochondria in cardiomyocytes (0.514 +/- 0.032% in tetradecylthioacetic acid v 0.318 +/- 0.007% in control) which was due to an increased size of mitochondria [18].

Associations of Lopac-T-1698 with other chemical compounds

• The present work shows that when mitochondrial beta-oxidation is stimulated by the hypolipemic, non-beta-oxidizable fatty acid analogue tetradecylthioacetic acid, there is a decrease in the secretion of triacylglycerol in cultured rat hepatocytes [19].
• Administration of tetradecylthioacetic acid resulted in a dramatic decrease in proliferation and a robust upregulation of the expression of involucrin and transglutaminase [17].
• At the highest concentration of fatty acid used (64 microM) tetradecylthioacetic acid was found to be the most effective of all fatty acids tested in inhibiting cell growth, whilst palmitic acid and docosahexaenoic acid had no significant effect on cell growth [20].
• In addition, we demonstrate that suppression of rat hepatic HMG-CoA reductase activity during treatment with tetradecylthioacetic acid may contribute to a cholesterol-lowering effect [21].
• A practical procedure is described for the quantitative measurement of the amount of acyl units derived from tetradecylthioacetic acid (effecting hypolipemia in rats) and tetradecylthiopropionic acid (effecting hyperlipidemia) [22].

Gene context of Lopac-T-1698

• In mice orally treated with the novel, highly selective, and potent PPARalpha agonists GW 7647, GW 6867, and tetradecylthioacetic acid, Abcd2 expression was induced in liver and adrenal glands, but not in brain and testis [23].
• Antiinflammatory effects of tetradecylthioacetic acid involve both peroxisome proliferator-activated receptor alpha-dependent and -independent pathways [24].
• TTA also activates the other PPARs (e.g., PPAR delta) and this might compensate for deficiency of PPAR alpha [25].
• (iii) Tetradecylthioacetic acid increased the cytokine stimulating effects of tumour necrosis factor alpha with a particularly enhancing effect on IL-10 [26].
• Altogether, TTA-mediated clearance of blood triglycerides may result from a lowered level of apo C-III, with a subsequently induction of hepatic lipoprotein lipase activity and (re)uptake of fatty acids from very low density lipoprotein (VLDL) [25].

Analytical, diagnostic and therapeutic context of Lopac-T-1698

• OBJECTIVE: The sulfur containing tetradecylthioacetic acid (TTA) has a profound effect on lipid metabolism and may also exert antioxidant and anti-inflammatory actions and thereby counteract coronary stenosis after angioplasty balloon injury [27].
• Growth reduction in glioma cells after treatment with tetradecylthioacetic acid: changes in fatty acid metabolism and oxidative status [28].
• Tetradecylthioacetic acid reduces stenosis development after balloon angioplasty injury of rabbit iliac arteries [29].
• Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV-infected patients on highly active antiretroviral therapy [30].
• Changes in [3H]thymidine incorporation preceded changes in cell number in TTA-treated glioma cell cultures, and the growth inhibition was more significantly expressed by [3H]thymidine incorporation than cell number [9].

References