Potent inhibitory effect of trans9, trans 11 isomer of conjugated linoleic acid on the growth of human colon cancer cells
Potent inhibitory effect of trans9, trans 11 isomer of conjugated linoleic acid on the growth of human colon cancer cells
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DOI：
10.1016/j.jnutbio.2006.01.007
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发表时间：
2006-12-01
影响因子：
5.6
通讯作者：
Miyashita, Kazuo
中科院分区：
文献类型：
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作者：
Beppu, Fumiaki;Hosokawa, Masashi;Miyashita, Kazuo
本研究比较了纯共轭亚油酸（CLA）异构体[顺式(c)9、c11-CLA、c9、反式(t)11-CLA、t9、t11-CLA和t10、c12-CLA]对人结肠癌细胞株（cco -2、HT-29和DLD-1）的生长抑制作用。当caco2细胞与200 μ M孵育72 h时，即使在10%胎牛血清（FBS）存在的情况下，所有CLA异构体也能以时间依赖性的方式抑制细胞增殖。抑制作用最强的是t9、t11-CLA，其次是t10、c12-CLA、c9、c11-CLA和c9、t11-CLA。t9、t11-CLA在其他结肠癌细胞系（HT-29和DLD-1）中也有最强的作用。在1% FBS存在下，确定了CLA异构体的抑制作用顺序。培养基中添加的CLA异构体很容易融入Caco-2的细胞脂质中，并改变其脂肪酸组成。细胞脂质中CLA含量分别为t9、t11-CLA 26.2 +/- 2.7%、c9、t11-CLA 35.9 +/- 0.3%和t10、c12-CLA 46.3 +/- 0.8%。在t9，t11-CLA处理的Caco-2细胞中可以清楚地识别DNA断裂。t9、t11-CLA的凋亡作用具有剂量和时间依赖性。9c，11t-CLA和t10，c12-CLA也能诱导DNA断裂。然而，这两种异构体的破碎程度都远低于t9，t11-CLA。t9t11-CLA处理Caco-2细胞降低与凋亡相关的Bcl-2水平，而Bax水平保持不变。这些结果表明，t9t11-CLA降低Bcl-2的表达可能会增加细胞对脂质过氧化和程序性细胞死亡、凋亡的敏感性。(c) 2006爱思唯尔公司版权所有。
This study compared the growth inhibitory effects of pure conjugated linoleic acid (CLA) isomers [cis(c)9,c11-CLA, c9,trans(t)11-CLA, t9,t11-CLA, and t10,c12-CLA] on human colon cancer cell lines (Caco-2, HT-29 and DLD-1). When Caco-2 cells were incubated up to 72 h with 200 mu M, each isomer, even in the presence of 10% fetal bovine serum (FBS), cell proliferation was inhibited by all CLA isomers in a time-dependent manner. The strongest inhibitory effect was shown by t9,t11-CLA, followed by t10,c12-CLA, c9,c11-CLA and c9,t11-CLA, respectively. The strongest effect of t9,t11-CLA was also observed in other colon cancer cell lines (HT-29 and DLD-1). The order of the inhibitory effect of CLA isomer was confirmed in the presence of 1% FBS. CLA isomers supplemented in the culture medium were readily incorporated into the cellular lipids of Caco-2 and changed their fatty acid composition. The CLA contents in cellular lipids were 26.2 +/- 2.7% for t9,t11-CLA, 35.9 +/- 0.3% for c9,t11-CLA and 46.3 +/- 0.8% for t10,c12-CLA, respectively. DNA fragmentation was clearly recognized in Caco-2 cells treated with t9,t11-CLA. This apoptotic effect of t9,t11-CLA was dose- and time-dependent. DNA fragmentation was also induced by 9c,11t-CLA and t10,c12-CLA. However, fragmentation levels with both isomers were much lower than that with t9,t11-CLA. t9t11-CLA treatment of Caco-2 cells decreased Bcl-2 levels in association with apoptosis, whereas Bax levels remained unchanged. These results suggest that decreased expression of Bcl-2 by t9t11-CLA might increase the sensitivity of cells to lipid peroxidation and to programmed cell death, apoptosis. (c) 2006 Elsevier Inc. All rights reserved.