The type rather than the amount of
dietary fat may be more important in breast
carcinogenesis. While animal studies support this view, little is known about the effects of
essential fatty acids (EFAs) at the cellular level. The MCF-7
breast cancer and the MCF-10A non-cancerous human mammary epithelial cell lines are compared in terms of growth response to EFAs and ability to incorporate and process the EFAs. Eicosapentaenoic (EPA, n-3) and docosahexaenoic (DHA, n-3)
acids, presented bound to
albumin, inhibited the growth of MCF-7 cells by as much as 50% in a dose-dependent manner (6-30 microM) 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 levels below 24 microM. The differential effects of AA, EPA and DHA on MCF-7 and MCF-10A cells support a protective role of highly unsaturated
essential fatty acids against
breast cancer. The EFAs were primarily incorporated into
phosphoglycerides. MCF-7 cells showed chain elongations and possibly delta 8 desaturation, but no AA was formed from LA, nor EPA or DHA from LNA. In contrast, MCF-10A cells desaturated and elongated the exogenous EFAs via all the known pathways. These findings suggest defects in the desaturating
enzymes of MCF-7 cells. LNA, DHA and AA presented to MCF-7 cells in
phospholipid liposomes inhibited growth as extensively as
albumin-bound free
acids, but were less extensively incorporated, suggesting different mechanisms of inhibition for the two methods.