Milk fat conjugated linoleic acid (CLA) inhibits growth of human mammary MCF-7 cancer cells

The relationship between growth and the antioxidant enzyme defence system i n human MCF-7 (breast) cancel cells treated with bovine milk far enriched w ith conjugated linoleic acid (CLA) was studied Milk enriched in CLA was obt ained from cows on pasture supplemented with full fat rapeseeds and full fa t soyabeans (I). Cell number decreased rip to 90 % (p < 0.05) and lipid per oxidation inn eased 15- fold (p < 0.05) following incubation of MCF-7 cells for 8 days with increasing levels of milk fat yielding CLA concentrations between 16.9 and 22.6 ppm. Growth suppression and prooxidant effects of mil k fat CLA were independent of the variable composition of the milk fat samp les, suggesting that CLA was the active ingredient in milkfat responsible f or the cytotoxic effect. Mixtures containing isomers of CLA (c9, t11; t10, c12; c11, t13- and minor amounts of other isomers) and linoleic acid (LA) a t similar concentrations to the milk fat samples were as effective at inhib iting growth and stimulating peroxidation of MCF-7 cells as the milk fatty acids. Incubation of the cells with the c9, t11 CLA isomer (20 ppm) or the mixture of CLA isomers (20 ppm) for 8 days resulted in a 60 % decrease (p < 0.05) in viability compared with untreated controls and was significantly (p < 0.05) more effective than incubation with the t10, c12 CLA isomer (20 ppm), which caused only a 15 % decrease in cell numbers under similar condi tions. A 25 % increase (p < 0.05) in cell proliferation occurred when LA (2 0 ppm) alone was incubated with MCF-7 cells for 8 days. C-14-CLA was prefer entially incorporated into the phospholipid fraction of the MCF-7 cell lipi ds in a dose-dependent manner and CLA accumulated in cell membranes more ef ficiently when the cells were incubated ir? the presence of milk fat than t he c9, t11 synthetic CLA isomer. Superoxide dismutase (SOD), catalase and g lutathione pet-oxidase (GPx) activities weve induced in MCF-7 cells exposed to milk fat (containing 16.9-22.6 ppm CLA) over 8 days. The data indicate that milk fat triglyceride-bound CLA, consisting primarily of the c9, t11 i somer, was cytotoxic towards MCF-7 cells.