Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol
Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol
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DOI：
10.1016/j.bbrc.2006.07.029
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发表时间：
2006-09-15
影响因子：
3.1
通讯作者：
Miyazawa, Teruo
中科院分区：
文献类型：
--
作者：
Eitsuka, Takahiro;Nakagawa, Kiyotaka;Miyazawa, Teruo
由于大多数癌细胞中检测到高端粒酶活性，通过药物或膳食成分抑制端粒酶是预防癌症的新策略。在这里，我们研究了维生素E的抑制作用，特别强调生育三烯酚（不饱和维生素E），在细胞培养研究中对人端粒酶。结果表明，生育三烯酚对DLD-1人结肠癌细胞端粒酶活性的抑制作用呈时间和剂量依赖性，其中5-生育三烯酚的抑制作用最强。生育三烯酚抑制蛋白激酶C活性，导致delta-myc和人端粒酶逆转录酶（hTERT）表达下调，从而降低端粒酶活性。与生育三烯酚相反，生育酚显示出非常弱的端粒酶抑制。这些结果首次提供了新的证据，表明生育三烯酚作为一个有效的候选调节端粒酶和支持生育三烯酚的抗增殖功能。(c)2006年爱思唯尔公司All rights reserved.
As high telomerase activity is detected in most cancer cells, inhibition of telomerase by drug or dietary food components is a new strategy for cancer prevention. Here, we investigated the inhibitory effect of vitamin E, with particular emphasis on tocotrienol (unsaturated vitamin E), on human telomerase in cell-culture study. As results, tocotrienol inhibited telomerase activity of DLD-1 human colorectal adenocarcinoma cells in time- and dose-dependent manner, interestingly, with 5-tocotrienol exhibiting the highest inhibitory activity. Tocotrienol inhibited protein kinase C activity, resulting in down-regulation of delta-myc and human telomerase reverse transcriptase (hTERT) expression, thereby reducing telomerase activity. In contrast to tocotrienol, tocopherol showed very weak telomerase inhibition. These results provide novel evidence for the first time indicating that tocotrienol acts as a potent candidate regulator of telomerase and supporting the anti-proliferative function of tocotrienol. (c) 2006 Elsevier Inc. All rights reserved.