N-3 AND N-6 FATTY-ACID PROCESSING AND GROWTH EFFECTS IN NEOPLASTIC AND NON-CANCEROUS HUMAN MAMMARY EPITHELIAL-CELL LINES

The type rather than the amount of dietary fat may be more important i n breast carcinogenesis. While animal studies support this view, littl e is known about the effects of essential fatty acids (EFAs) at the ce llular level. The MCF-7 breast cancer and the MCF-10A non-cancerous hu man mammary epithelial cell lines are compared in terms of growth resp onse to EFAs and ability to incorporate and process the EFAs. Eicosape ntaenoic (EPA, n-3) and docosahexaenoic (DHA, n-3) acids, presented bo und to albumin, inhibited the growth of MCF-7 cells by as much as 50% in a dose-dependent manner (6-30 mu M) in medium containing 0.5% serum . alpha-Linolenic (LNA, n-3) and arachidonic (AA, n-6) acids inhibited growth less extensively, while linoleic acid (LA, n-6) had no effect. In contrast, MCF-10A cells were not inhibited by any of the EFAs at l evels below 24 mu M. The differential effects of AA, EPA and DHA on MC F-7 and MCF-10A cells support a protective role of highly unsaturated essential fatty acids against breast cancer. The EFAs were primarily i ncorporated into phosphoglycerides. MCF-7 cells showed chain elongatio ns and possibly Delta(8) desaturation, but no AA was formed from LA, n or EPA or DHA from LNA. In contrast, MCF-10A cells desaturated and elo ngated the exogenous EFAs via all the known pathways. These findings s uggest defects in the desaturating enzymes of MCF-7 cells. LNA, DHA an d AA presented to MCF-7 cells in phospholipid liposomes inhibited grow th as extensively as albumin-bound free acids, but were less extensive ly incorporated, suggesting different mechanisms of inhibition for the two methods.