Development of cancer preventing agent using conjugated trienoic fatty acids

我们发现，共轭二十碳五烯酸（CEPA）和共轭二十二碳六烯酸（CDHA）对人肿瘤细胞系的选择性杀伤作用最强。这些共轭脂肪酸的掺入足以增加对氧化损伤的敏感性，这表明凋亡细胞死亡。经碱性处理制备的三烯结构CEPA对雄性胸腺裸鼠ddd -1细胞（结直肠癌）移植瘤具有强烈的毒性。其抗癌活性与膜磷脂过氧化有关。CEPA在裸鼠DLD-1细胞移植瘤中诱导DNA断裂，提示凋亡参与其抗癌机制。研究证实，饲喂1% （w/w %）骨酸（ESA, 9,11,13 -18:3）饲料的大鼠肝脏和血浆中存在大量的9,11 -共轭亚油酸（CLA, 9,11 -18:2）。9,11 - cla转化为4,4 -二甲基氯唑啉衍生物后，采用气相色谱-电子冲击质谱法对其化学结构进行了鉴定。CLA在肝脏总脂肪酸和血脂中的浓度在补充CLA的大鼠中分别达到1%，而在补充esa的大鼠中分别达到3.2%和2.5%。α-ESA在大鼠体内通过δ 13饱和反应被部分代谢为CLA。在α-ESA喂养的动物中观察到的一些生物活性也可归因于体内由ESA形成的CLA。

We found out that conjugated eicosapentaenoic acid (CEPA) and conjugated docosahexaenoic acid (CDHA) with conjugated trienoic structure, have the strongest cytotoxic effect selectively on human tumor cell lines. The incorporation of these conjugated fatty acids is sufficient to increase the sensitivity to oxidative damage that is indicative for apoptotic cell death. The CEPA with triene structure, prepared by aikaline treatment, showed intensive toxicity with DLD-1 cell (colorectal adenocarcinoma) -transplanted tumor in male athymic nude mice. The anticarcinogenic activity involved membrane phospholipid peroxidation. CEPA induced DNA fragmentation in DLD-1 cell-transplanted tumor in nude mice, indicating the involvement of apoptosis in the anticarcinogenic mechanism.The occurrence of a significant amount of 9, 11-conjugated linoleic acid (CLA, 9, 11-18:2) was confirmed in the liver and plasma lipids of rats fed a 1% (w/w % of diet) eleostearic acid (ESA, 9, 11, 13-18:3) diet. The chemical structure of 9, 11-CLA was identified by gas chromatography-electron impact mass spectrometry after its conversion to a 4, 4-dimethyloxazoline derivative. The concentration of CLA in the total fatty acids of the liver and plasma lipids reached to 1% for each in the CLA-supplemented rats, while reaching 3.2% and 2.5%, respectively, in the ESA-supplemented rats. The α-ESA was shown to be metabolized partially to CLA via a delta 13-saturation reaction in the rat. Some biological activities observed in α-ESA-fed animals may be ascribed also to CLA that is formed from ESA in the body.