Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane.
Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane.
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DOI：
10.1186/1476-511x-10-73
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发表时间：
2011-05-12
影响因子：
4.5
通讯作者：
Rizzo AM
中科院分区：
文献类型：
--
作者：
Corsetto PA;Montorfano G;Zava S;Jovenitti IE;Cremona A;Berra B;Rizzo AM
多不饱和脂肪酸是膜秩序和功能的重要分子，它们可以调节炎症诱导的细胞因子的产生、二十烷类化合物的产生、血浆三酰甘油的合成和基因表达。最近的研究表明，n-3多不饱和脂肪酸可以作为癌症的化学预防、化学抑制和癌症治疗的辅助药物。N-3多不饱和脂肪酸可以改变肿瘤生长，影响细胞复制、细胞周期和细胞死亡。有待回答的问题是，n-3多不饱和脂肪酸如何影响如此多的生理过程。我们假设n-3多不饱和脂肪酸改变了细胞膜的稳定性，改变了乳腺癌细胞中的细胞信号。用AA、EPA和DHA处理两株ER和EGFR受体表达不同的人乳腺癌细胞。我们通过四甲基偶氮唑盐活性试验和细胞凋亡标记物的表达来评估多不饱和脂肪酸对肿瘤生长的影响。用高效液相色谱分析磷脂，以评估n-3掺入细胞膜。我们观察到，EPA和DHA诱导细胞凋亡，细胞活力降低，bcl2和proaspase-8表达减少。此外，DHA略微降低了EGFR的浓度，而EPA则无此作用。EPA和DHA均可降低EGFR的活性。N-3脂肪酸在两种细胞系中都部分代谢；AA是整合的，不会进一步代谢。我们已经分析了膜磷脂中的脂肪酸模式，其中它们以不同程度的特异性结合在一起。N-3多不饱和脂肪酸影响n-6含量，反之亦然。我们的结果表明，n-3多不饱和脂肪酸可能导致乳腺癌细胞膜结构的改变，从而增加了脂肪酸的不饱和度。这篇文章强调了营养因素对健康维护和疾病预防的重要性。
PUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells. Two lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane. We have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and the expression of Bcl2 and procaspase-8. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR. N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa. Our results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.