Effects of Fatty Acids and Inhibitors of Eicosanoid Synthesis on the Growth of a Human Breast Cancer Cell Line in Culture¹

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 ω6 FA, stimulated MDA-MB-231 cell growth with an optimal effect at a concentration of 0.75 µg/ml, whereas oleic acid, an ω9 FA, produced growth stimulation at 0.25 µg/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 µg/ml; eicosapentaenoic acid, also an ω3 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 µg/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.