Eicosapentaenoic acid and sulphur substituted fatty acid analogues inhibit the proliferation of human breast cancer cells in culture.
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.
Abdi-Dezfuli
F
F
Department of Clinical Biology, University of Bergen, Haukeland Hospital, Norway.
Frøyland
L
L
Thorsen
T
T
Aakvaag
A
A
Berge
R K
RK
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D013440:Sulfides / Q000494:pharmacology; D013457:Sulfur Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000975:Antioxidants; D005227:Fatty Acids; D016877:Oxidants; D013440:Sulfides; D013457:Sulfur Compounds; D016718:Arachidonic Acid; D019328:Buthionine Sulfoximine; C062078:1-(carboxymethylthio)tetradecane; D015118:Eicosapentaenoic Acid; D005978:Glutathione