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

Abstract

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.

Improved Antitumoral Activity of Extracts Derived from Cultured <i>Penicillus dumetosus</i>

“…Moreover, a variety of fatty acids and their derivatives have antiproliferative effects in different cancer cell models. In particular, polyunsaturated fatty acids (PUFAs) have been demonstrated to reduce proliferation and induce cell death in studies with leukemia cell lines [9]. In this study, we observed an increase in the PUFA content of P. dumetosus extracts during cultivation.…”

“…Recent studies have shown that both aqueous and organic extracts of Penicillus dumetosus exhibit in vitro antiprotozoal [5,6], as well as cytotoxic and antiproliferative activities on cancer cell lines [7]. In some cases, the antiproliferative activity of marine alga extracts has been positively correlated with the total polyphenol content suggesting a causal link related to extract content of polyphenols and phenolic acids [8], while other authors have reported a variety of fatty acids and derivatives with antiproliferative effects in different cancer cell models [9].…”

Effect of dietary tetradecylthioacetic acid on colon cancer growth studied by dynamic contrast enhanced MRI

“…Tetradecylthioacetic acid (TTA) is a bioactive fatty acid with a sulphur atom inserted in the 3 position from the carboxylic end (CH 3 -(CH 2 ) 13 -S-CH 2 COOH), the metabolic effects of TTA has recently been reviewed. 13 TTA has been shown to have an antiproliferative potency in cell lines such as glioma, leukemia and breast cancer, [14][15][16] as well as in vivo. 17 TTA seems to trigger apoptosis through mechanisms mediated via the mitochondria and selective modulation of the mitochondrial redox equilibrium.…”

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

“…Numerous studies have been carried out and several reports have revealed that fatty acids and compounds modulating the fatty acid metabolism exert growth-limiting properties in a variety of cancer cells (4,5). One of these compounds is tetradecylthioacetic acid (TTA) [CH 3 -(CH 2 ) 13 -S-CH 2 -COOH], which is a sulfursubstituted fatty acid that has been shown to reduce proliferation of tumor cells (6)(7)(8)(9).…”