Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture.
Dietary lipids may influence breast cancer progression and prognosis. The MDA-MB-231 human breast cancer cell line was used to examine the direct effects of the various classes of free fatty acids (FAs) on growth in serum-free medium and the involvement of eicosanoid biosynthesis. Linoleic acid, an omega 6 FA, stimulated MDA-MB-231 cell growth with an optimal effect at a concentration of 0.75 microgram/ml, whereas oleic acid, an omega 9 FA, produced growth stimulation at 0.25 microgram/ml but was inhibitory at higher concentrations. Docosahexaenoic acid exhibited a dose-related inhibition of cell growth at concentrations ranging from 0.5 to 2.5 micrograms/ml; eicosapentaenoic acid, also an omega 3 FA, was less effective. Similar inhibitory effects occurred with saturated FAs. Indomethacin, which at high concentrations is an inhibitor of both the cyclooxygenase- and lipoxygenase-catalyzed pathways of eicosanoid synthesis, suppressed cell growth stimulation by an otherwise optimal dose of linoleic acid when present at 40 micrograms/ml. Experiments with piroxicam, nordihydroguaiaretic acid, and esculetin, other inhibitors of eicosanoid biosynthesis with varying selectivity for enzymes of the prostaglandin and leukotriene pathways, indicated that MDA-MB-231 cell growth was dependent on leukotriene rather than prostaglandin production.
Rose
D P
DP
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, New York 10595.
Connolly
J M
JM
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D015777:Eicosanoids / Q000502:physiology*; D005227:Fatty Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D010894:Piroxicam / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology; D014468:Umbelliferones / Q000494:pharmacology
D015777:Eicosanoids; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D014468:Umbelliferones; D010894:Piroxicam; D009637:Masoprocol; C007628:esculetin; D007213:Indomethacin