n-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines.
n-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines.
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N-3和N-6脂肪酸加工以及肿瘤和非癌性人类乳腺上皮细胞系中的生长效应。
DOI：
10.1038/bjc.1994.283
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发表时间：
1994-08
影响因子：
8.8
通讯作者：
Miller, W M
中科院分区：
文献类型：
--
作者：
Grammatikos, S I;Subbaiah, P V;Victor, T A;Miller, W M
在乳腺癌的发生中，膳食脂肪的类型而不是数量可能更重要。虽然动物研究支持这一观点，但对必需脂肪酸（EFA）在细胞水平上的作用知之甚少。比较MCF-7乳腺癌和MCF-10A非癌性人乳腺上皮细胞系对EFA的生长反应以及掺入和加工EFA的能力。二十碳五烯酸（EPA，n-3）和二十二碳六烯酸（DHA，n-3），结合到白蛋白，抑制MCF-7细胞的生长高达50%，在含有0.5%血清的培养基中，以剂量依赖性的方式（6-30 μ M）。α-亚麻酸（LNA，n-3）和花生四烯酸（AA，n-6）对生长的抑制作用较小，而亚油酸（LA，n-6）则无影响。相比之下，MCF-10A细胞在低于24 μ M的水平下不被任何EFA抑制。AA，EPA和DHA对MCF-7和MCF-10A细胞的不同作用支持高度不饱和必需脂肪酸对乳腺癌的保护作用。EFA主要掺入磷酸甘油酯中。MCF-7细胞显示出链延长和可能的δ 8去饱和，但LA没有形成AA，LNA也没有形成EPA或DHA。相比之下，MCF-10A细胞通过所有已知的途径去饱和并延长外源EFA。这些发现表明MCF-7细胞的去饱和酶存在缺陷。LNA，DHA和AA提出的MCF-7细胞在磷脂脂质体中抑制生长广泛的白蛋白结合的游离酸，但不太广泛的纳入，这表明不同的机制的抑制两种方法。
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.