PROLIFERATIVE RESPONSES OF NORMAL HUMAN MAMMARY AND MCF-7 BREAST-CANCER CELLS TO LINOLEIC-ACID, CONJUGATED LINOLEIC-ACID AND EICOSANOID SYNTHESIS INHIBITORS IN CULTURE

Potential mechanisms for the stimulation or inhibition of cell growth by linoleic acid (LA) and conjugated linoleic acid (CLA) were investig ated by using eicosanoid synthesis inhibitors. Normal human mammary ep ithelial cells (HMEC) and MCF-7 breast cancer cells were incubated in serum-free medium supplemented with LA and CLA and cyclooxygenase (ind omethacin; INDO) or lipoxygenase (nordihydroguaiaretic acid; NDGA) inh ibitors. Linoleic acid stimulated the growth and [H-3]thymidine incorp oration of normal HMEC and MCF-7 cancer cells, while CLA was inhibitor y. Supplementation with LA increased intracellular lipid peroxide conc entrations in normal HMEC and MCF-7 cancer cells, whereas CLA did not affect lipid peroxide formation. Normal HMEC and MCF-7 cells supplemen ted with LA and INDO or NDGA resulted in growth inhibition. The treatm ent of normal HMEC with CLA and INDO or NDGA, and MCF-7 cells with CLA and INDO stimulated cell growth. However, the addition of CLA and NDG A to MCF-7 cells resulted in synergistic growth suppression suggesting that CLA effects were mediated through lipoxygenase inhibition. Altho ugh NDGA was more inhibitory of cell growth in the presence of LA or C LA than INDO, growth was associated with both prostaglandin and leukot riene production. Additional studies are warranted to elucidate the me chanism(s) whereby LA or CLA affect breast cell growth.