EFFECTS OF FATTY-ACIDS AND INHIBITORS OF EICOSANOID SYNTHESIS ON THE GROWTH OF A HUMAN BREAST-CANCER CELL-LINE IN CULTURE

  • 15 November 1990
    • journal article
    • research article
    • Vol. 50  (22) , 7139-7144
Abstract
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 .mu.g/ml, whereas oleic acid, an .omega.9 FA, produced growth stimulation at 0.25 .mu.g/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 .mu.g/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 .mu.g/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 prostanglandin production.