Eicosapentaenoic acid and sulphur substituted fatty acid analogues inhibit the proliferation of human breast cancer cells in culture

Abstract

Numerous studies have shown dietary fatty acids to influence the progression of several types of cancers. The purpose of the present investigation was to examine the influence of various types of fatty acids, including omega-3 fatty acids and a new class of hypolipidemic peroxisome proliferating fatty acid analogues, namely the 3-thia fatty acids, on MCF-7 human breast cancer cell growth. 3-thia fatty acids represent non-beta-oxidizable fatty acid analogues in which a sulphur atom substitutes for the beta-methylene group (3-position) in the saturated and unsaturated fatty acids. The effects of increasing concentrations of palmitic acid, tetradecylthioacetic acid (a 3-thia fatty acid), eicosapentaenoic acid, docosahexaenoic acid, and two 3-thia polyunsaturated fatty acids on the proliferation of MCF-7 cells, maintained in serum-free culture, were studied. 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. Thus, of the two dietary polyunsaturated omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid, only eicosapentaenoic acid possesses an inhibitory effect on the proliferation of MCF-7 cells. In all cases the inhibitory effect of the fatty acid was found to be reversible. Tetradecylthioacetic acid has been shown to be a potent peroxisome proliferator. It was, therefore, hypothesized that tetradecylthioacetic acid may inhibit the human MCF-7 cell growth by increasing the level of oxidative stress within the cell. However, use of agents which modify the cell's protective apparatus against oxidative stress had no influence on the inhibitory effect of tetradecylthioacetic acid. These experiments indicate that tetradecylthioacetic acid inhibits cell growth by mechanisms which may be independent of oxidative status.

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

“…The capacity of TTA to inhibit cancer cell growth is pronounced when compared with normal fatty acids such as PA (6,7). This might be related to their capacity to modulate mitochondrial oxidation and thereby lipid accumulation.…”

“…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).…”

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.…”

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

“…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.…”