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

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 u>6FA, stimulated MDA-MB-231 cell growth with an optimal effect at a concentration of 0.75 Mg/ml,whereas oleic acid, an ..•') FA, produced growth stimulation at 0.25 u«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 ut;,nil: eicosapentaenoic acid, also an <u3FA, was less effective. Similar inhibi tory effects occurred with saturated FAs. Indomethacin, which at high concentrations is an inhibitor of both the cyclooxygenaseand lipoxygenase-catalyzed pathways of eicosanoid synthesis, suppressed cell growth stimulation by an otherwise optimal dose of linoleic acid when present at 40 yg/ml. Experiments with piroxicam, nordihydroguaiaretic acid, and esculetin, other inhibitors of eicosanoid biosynthesis with varying selec tivity for enzymes of the prostaglandin and leukotriene pathways, indi cated that MDA-MB-231 cell growth was dependent on leukotriene rather than prostaglandin production.