Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apoptosis and inhibits growth of colo 201 human colon cancer cells
Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apoptosis and inhibits growth of colo 201 human colon cancer cells
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DOI：
10.1207/s15327914nc5001_10
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发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Tsubura, A
中科院分区：
文献类型：
--
作者：
Danbara, N;Yuri, T;Tsubura, A
在科洛201人结肠癌细胞系中检测了共轭二十二碳六烯酸（CDHA）对结肠癌细胞生长的抑制作用，并将该作用与二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）进行了比较。通过比色3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑（MTS）测定，CDHA是比DHA和EPA更有效的肿瘤细胞生长抑制剂（72小时的IC 50分别为31.6 μ M、468 μ M和566 μ M）。CDHA抑制细胞周期进程，由于细胞在G1期的积累，这涉及增加p21（Cip 1/Waf 1）和减少细胞周期蛋白D1，细胞周期蛋白E和增殖细胞核抗原表达; p53和细胞周期蛋白A水平不变。亚G1群体的出现证实了细胞凋亡的诱导，细胞凋亡级联反应涉及细胞凋亡增强蛋白（巴克和Bcl-x（S））的上调和细胞凋亡抑制蛋白（Bcl-x（L）和Bcl-2）的下调。CDHA调节细胞周期调节蛋白和凋亡相关蛋白，类似于DHA的作用。CDHA在1.0%的膳食剂量下显著抑制裸鼠移植的科洛201细胞的生长。
The effect of conjugated docosahexaenoic acid (CDHA) on the inhibition of colon cancer cell growth was examined in the colo 201 human colon cancer cell line, and the effect was compared with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). CDHA was a more potent tumor cell growth inhibitor than DHA and EPA by colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay (IC50 for 72 h: 31.6 muM, 468 muM, and 566 muM, respectively). CDHA inhibited cell cycle progression, due to accumulation of cells in G1 phase, which involved increased p21(Cip1/Waf1) and decreased cyclin D1, cyclin E, and proliferating cell nuclear antigen expression; the p53 and cyclin A levels were unchanged. Induction of apoptosis was confirmed by the appearance of sub-G1 populations, and apoptosis cascade involved upregulation of the apoptosis-enhancing proteins (Bak and Bcl-x(S)) and downregulation of the apoptosis-suppressing proteins (Bcl-x(L) and Bcl-2). CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins, similar to the effects of DHA. CDHA at a dietary dose of 1.0% significantly inhibited growth of colo 201 cells transplanted in nude mice.