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

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Abstract

Numerous studies have shown dietary fatty acids toinfluence the progression of several types of cancers.The purpose of the present investigation was toexamine the influence of various types of fattyacids, including ω-3 fatty acids and a newclass of hypolipidemic peroxisome proliferating fatty acid analogues,namely the 3-thia fatty acids, on MCF-7 humanbreast cancer cell growth. 3-thia fatty acids representnon-β-oxidizable fatty acid analogues in which a sulphuratom substitutes for the β-methylene group (3-position) inthe 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 acidson the proliferation of MCF-7 cells, maintained inserum-free culture, were studied. At the highest concentrationof fatty acid used (64 µM) tetradecylthioacetic acidwas found to be the most effective ofall fatty acids tested in inhibiting cell growth,whilst palmitic acid and docosahexaenoic acid had nosignificant effect on cell growth. Thus, of thetwo dietary polyunsaturated ω-3 fatty acids eicosapentaenoic acidand docosahexaenoic acid, only eicosapentaenoic acid possesses aninhibitory effect on the proliferation of MCF-7 cells.In all cases the inhibitory effect of thefatty acid was found to be reversible.Tetradecylthioacetic acid has been shown to be apotent peroxisome proliferator. It was, therefore, hypothesized thattetradecylthioacetic acid may inhibit the human MCF-7 cellgrowth by increasing the level of oxidative stresswithin the cell. However, use of agents whichmodify the cell's protective apparatus against oxidative stresshad no influence on the inhibitory effect oftetradecylthioacetic acid.These experiments indicate that tetradecylthioacetic acid inhibits cellgrowth by mechanisms which may be independent ofoxidative status.

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Abdi-Dezfuli, F., Frøyland, L., Thorsen, T. et al. Eicosapentaenoic acid and sulphur substituted fatty acid analogues inhibit the proliferation of human breast cancer cells in culture. Breast Cancer Res Treat 45, 229–239 (1997). https://doi.org/10.1023/A:1005818917479

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