Stillwell W, Ehringer W, Jenski L J
Department of Biology, Indiana University-Purdue University, Indianapolis 46202-5132.
Lipids. 1993 Feb;28(2):103-8. doi: 10.1007/BF02535772.
Docosahexaenoic acid (DHA), a long-chain polyunsaturated omega 3 fatty acid, is tested to determine its mode of action as an anti-cancer agent. We demonstrate that DHA can increase the permeability of phospholipid vesicles, as monitored by vesicle swelling in isosmolar erythritol and leakage of sequestered carboxyfluorescein, and T27A tumor cells, as monitored by swelling in isosmolar erythritol and release of sequestered 51Cr. DHA was incorporated into lipid vesicles as either the free fatty acid or as 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine. DHA was incorporated into the tumor cells by fusion with vesicles made from the mixed-chain phosphatidylcholines. DHA is demonstrated here to be much more effective in increasing permeability than is oleic acid, the major unsaturated fatty acid normally found in tumor plasma membranes. It is proposed that incorporation of DHA makes tumor plasma membranes substantially more permeable, which may explain, in part, its anti-tumor properties.
二十二碳六烯酸（DHA）是一种长链多不饱和ω-3脂肪酸，现对其作为抗癌剂的作用模式进行研究。我们发现，通过等渗赤藓糖醇中的囊泡肿胀以及被隔离的羧基荧光素泄漏来监测，DHA可增加磷脂囊泡的通透性；通过等渗赤藓糖醇中的肿胀以及被隔离的51Cr释放来监测，DHA也可增加T27A肿瘤细胞的通透性。DHA以游离脂肪酸形式或1-硬脂酰-2-二十二碳六烯酰-sn-甘油-3-磷酸胆碱形式被整合到脂质囊泡中。DHA通过与由混合链磷脂酰胆碱制成的囊泡融合而被整合到肿瘤细胞中。研究表明，DHA在增加通透性方面比油酸有效得多，油酸是肿瘤质膜中通常存在的主要不饱和脂肪酸。有人提出，DHA的整合使肿瘤质膜的通透性大大增加，这可能部分解释了其抗肿瘤特性。
