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

被引:129
作者
GRAMMATIKOS, SI
SUBBAIAH, PV
VICTOR, TA
MILLER, WM
机构
[1] NORTHWESTERN UNIV, DEPT CHEM ENGN, EVANSTON, IL 60208 USA
[2] RUSH MED COLL, DEPT BIOCHEM, CHICAGO, IL 60612 USA
[3] RUSH MED COLL, DEPT MED, CHICAGO, IL 60612 USA
[4] NORTHWESTERN UNIV, EVANSTON HOSP, SCH MED, DEPT PATHOL, EVANSTON, IL 60201 USA
关键词
D O I
10.1038/bjc.1994.283
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 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 levels below 24 mu M. 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.
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页码:219 / 227
页数:9
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