Tetradecylthioacetic acid

There are other synthetic and natural thiolic compounds possessing antioxidant activity. One such compound is tetradecylthioacetic acid (TTA), which inhibited the iron-ascorbate-induced microsomal lipid peroxidation [234]. Its Se analog exhibited even a more profound antioxidative effect. 

Westergaard, M. etal. Modulation of keratinocyte gene expression and differentiation by PPAR selective ligands tetradecylthioacetic acid, J. Invest Dermatol., 116, 702, 2001. 

Addition of tetradecylthioacetic acid (TTA) to isolated rat hepatocytes leads to an increase in oxidation of palmitate and a strong decrease in de novo synthesis of fatty acids and cholesterol (Risan, K.A. Spydevold, 0., impublished results). Hepatocytes isolated from rats 24 hours after administration of TTA show also an elevated activity of CPT I. However, little is known about the acute effects of 3-thia fatty acids. 

When 3-thia fatty acids are added to isolated hepatocytes they stimulate fatty acid oxidation (Fig. 1). The strength of this effect depends on the chain length of 3-thia fatty acid used. Dodecylthioacetic acid (DTA) and tetradecylthioacetic acid (TTA) are most potent, shorter and longer 3-thia fatty acids have a reduced effect. 

Skrede, S. Bremer, J. 1993. Biochim. Biophys. Acta 1167 189-196. Acylcarnitine formation and fatty acid oxidation in hepatocytes from rats treated with tetradecylthioacetic acid (a 3-thia fatty acid). 

Thia fatty acids have been used as tools in experimental models to further penetrate the mechanisms of the lipid metabolism. These fatty acids are activated to their respective CoA-esters, but, they cannot be degraded by 3-oxidation because of the sulfur substitution in 3-position (reviewed ). Tetradecylthioacetic acid (TTA), a representative member of the 3-thia family, has the chemical structure of palmitic acid (C16) in which a sulfur atom is located between the 2 and 3-carbon atoms (COOH-CH2-S-(CH2)i3-CH3). TTA is a novel hypolipidemic drug which has been shown to combine several effects of CO-3 PUFAs, such as EPA, and structurally unrelated peroxisome proliferators, such as phenylacetate and fibrates. From this perspective we wanted to investigate if TTA shares the antitumor activity found for these functionally related compounds, and furthermore to study the metabolic effects of TTA in cancer cells in relation to the effects found in hepatocytes. 

Tetradecylthioacetic acid (TTA) is a fatty acid analogue in which a sulfur atom substitutes the P-methylene group of the alkyl chain. The analogue closely resembles normal fatty acids except that it is unable to be metabolized by P-oxidation. -3 fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also poorly oxidized and it has been reported that they inhibit proliferation of cancer cells in culture. Other similarities between TTA and < -3 fatty acids are induction of several enzymes involved in mitochondrial and peroxisomal P-oxidation. Moreover, they have hypotriglyceridemic effects, but TTA is much more potent than EPA. ... 

Figure 2. Effect of TTA on growth of human glioma spheroids. Abbreviations TTA, tetradecylthioacetic acid.

Tetradecylthioacetic acid (TTA) is a saturated fatty acid with a sulphur atom in the 3-position of the carbon chain. The sulphur atom in 3-position prevents TTA itself from being P-oxidized, but causes elevation of the general fatty acid oxidation. TTA was... 

Figure I. Structural formulas of eicos-apentaenoic acid (EPA) and different EPA-derivatives (all as ethyl esters), tetradecylthioacetic acid (TTA) and 2-methyl TTA.

Tetradecylthioacetic acid is a synthesised saturated fatty acid where a sulphur atom substitutes the third methylene group from the carboxylic end ... 

Rats treated with tetradecylthioacetic acid Hexeberg et al. (1995)... 

Abbreviations EPA, eicosapentaenoic acid TTA, tetradecylthioacetic acid. Values represent mean percentage s.d. p < 0.05 compared to control. Number of cells was measured by cell counting. MCF-7 growth data has been published by Abdi-Oezfuli, F. el al. 1997. ... 

---