Dipartimento di Scienze Molecolari Applicate ai Biosistemi, Università degli Studi di Milano, Italy.
Lipids Health Dis. 2011 May 12;10:73. doi: 10.1186/1476-511X-10-73.
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.
多不饱和脂肪酸（PUFAs）是膜有序性和功能的重要分子；它们可以调节炎症诱导的细胞因子产生、类二十烷酸产生、血浆三酰甘油合成和基因表达。最近的研究表明，n-3 PUFAs 可以作为癌症化学预防、化学抑制和癌症治疗的辅助剂。n-3 PUFAs 可以改变癌症的生长，影响细胞复制、细胞周期和细胞死亡。仍然需要回答的问题是 n-3 PUFAs 如何能影响如此多的生理过程。我们假设 n-3 PUFAs 通过改变膜稳定性来改变乳腺癌细胞中的细胞信号。
用 AA、EPA 或 DHA 处理两种不同 ER 和 EGFR 受体表达的人乳腺癌细胞系。我们使用 MTT 活力试验和凋亡标志物的表达来评估 PUFAs 对癌细胞生长的影响。通过 HPLC/GC 分析磷脂，以评估 n-3 掺入细胞膜的情况。
我们观察到 EPA 和 DHA 诱导细胞凋亡、降低细胞活力以及 Bcl2 和 procaspase-8 的表达。此外，DHA 略微降低了 EGFR 的浓度，但 EPA 没有影响。EPA 和 DHA 均能降低 EGFR 的激活。两种细胞系均部分代谢 n-3 脂肪酸；AA 被整合而不进一步代谢。我们分析了膜磷脂中的脂肪酸模式，它们以不同的特异性程度被整合。n-3 PUFAs 影响 n-6 的含量，反之亦然。
我们的结果表明，n-3 PUFAs 的喂养可能会引起乳腺癌细胞膜结构的改变，从而增加脂肪酸不饱和程度。本文强调了营养因素对维持健康和预防疾病的重要性。
