Tumor growth suppression by α-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation
Tumor growth suppression by α-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation
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DOI：
10.1093/carcin/bgh109
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发表时间：
2004-08-01
期刊：
影响因子：
4.7
通讯作者：
Miyazawa, T
中科院分区：
文献类型：
--
作者：
Tsuzuki, T;Tokuyama, Y;Miyazawa, T
我们以前已经证明，通过碱性异构化制备的共轭亚麻酸（CLnA）比共轭亚油酸（CLA）具有更强的抗肿瘤作用。在本研究中，我们用移植dpd -1人结肠癌细胞的裸鼠，比较了α -骨酸（α - esa, 9Z11E13E-18:3）与CLA异构体9Z11E-CLA和10E12Z-CLA对肿瘤生长的抑制作用。结果表明，α - esa是一种可以从天然来源批量制备的CLnA，具有比CLA更强的抗肿瘤作用。α - esa小鼠肿瘤组织DNA片段化增强，脂质过氧化作用增强，提示α - esa通过脂质过氧化作用诱导细胞凋亡。此外，用α - esa、9Z11E-CLA和10E12Z-CLA处理DLD-1细胞，证实α - esa在培养细胞系中具有比CLA更强的抗肿瘤作用。α - esa诱导细胞凋亡与α - esa处理后DNA片段化增强、caspase活性增加和caspase mRNA表达增加一致。添加α -生育酚，一种抗氧化剂，抑制氧化应激和细胞凋亡，表明这些作用与脂质过氧化有关。
We have previously shown that conjugated linolenic acids (CLnA) prepared by alkaline isomerization have a stronger antitumor effect than conjugated linoleic acids (CLA). In this study we have compared the suppressive effect on tumor growth of alpha-eleostearic acid (alpha-ESA, 9Z11E13E-18:3) with those of the CLA isomers 9Z11E-CLA and 10E12Z-CLA, using nude mice into which DLD-1 human colon cancer cells were transplanted. The results showed that alpha-ESA, which is a CLnA that can be prepared from natural sources in bulk, had a stronger antitumor effect than CLA. DNA fragmentation was enhanced and lipid peroxidation was increased in tumor tissues of the alpha-ESA-fed mice, which suggested that alpha-ESA induced apoptosis via lipid peroxidation. Furthermore, treatment of DLD-1 cells with alpha-ESA, 9Z11E-CLA and 10E12Z-CLA confirmed that alpha-ESA had a stronger antitumor effect than CLA in cultured cell lines. The induction of apoptosis by alpha-ESA was consistent with enhanced DNA fragmentation, increased caspase activity and increased expression of caspase mRNA following alpha-ESA treatment. Addition of alpha-tocopherol, an antioxidant, suppressed oxidative stress and apoptosis, suggesting that these effects were associated with lipid peroxidation.