Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines.

van de Mark K; Chen JS; Steliou KPerrine SPFaller DV

首页> 外文期刊>Journal of Cellular Physiology >Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines.

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Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines.

机译：α硫辛酸诱发p27Kip-dependent细胞细胞周期阻滞在非转换线细胞凋亡在肿瘤细胞系。

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alpha-Lipoic acid is a naturally-occurring co-factor found in a number of multi-enzyme complexes regulating metabolism. We report here that alpha-lipoic acid induces hyperacetylation of histones in vivo and has differential effects on the growth and viability of normal versus transformed cell lines. The human tumor cell lines FaDu and Jurkat, as well as a Ki-v-Ras-transformed Balb/c-3T3 murine mesenchymal cell line, all initiated apoptosis following exposure to alpha-lipoic acid. In contrast, treatment of non-transformed cell lines with alpha-lipoic acid resulted only in reversible cell cycle arrest in G0/G1. Treatment with butyrate, another short-chain fatty acid, induced a G0/G1 arrest in both transformed and non-transformed cell lines. alpha-Lipoic acid caused a post-translational elevation in the levels of the cyclin-dependent kinase inhibitor p27Kip1. Studies using p27Kip1-deficient MEF cells demonstrated that p27Kip1 was required for the alpha-lipoic acid-mediated cell cycle arrest. The mechanismof apoptosis was independent of Fas-mediated signaling, as alpha-lipoic acid-treated Jurkat cell mutants deficient in Fas or FADD retained sensitivity to apoptosis. The differential selectivity of the pro-apoptotic effects of alpha-lipoic acid for transformed cells supports its potential use in the treatment of neoplastic disorders.

机译：α硫辛酸是一种自然产生的辅助因子中发现许多工艺等复合物调节新陈代谢。α硫辛酸诱发hyperacetylation组蛋白在体内,微分作用在正常的生长和生存能力和转化细胞线。行FaDu Jurkat,以及Ki-v-Ras-transformed Balb / c-3T3小鼠间充质细胞,启动细胞凋亡暴露于α硫辛酸。相比之下,非转换细胞系α硫辛酸,但结果只有可逆细胞周期阻滞于G0 / G1。丁酸盐,另一个短链脂肪酸,诱导转化和G0 / G1逮捕非转换细胞系。引起了翻译后的海拔细胞周期蛋白依赖性激酶抑制剂的水平p27Kip1。细胞表明p27Kip1所需的α- acid-mediated细胞周期阻滞。发病的细胞凋亡是独立的Fas-mediated信号,如α-酸洗Jurkat细胞突变体在Fas不足或FADD保留对细胞凋亡的敏感性。微分pro-apoptotic的选择性α硫辛酸对转化的影响细胞支持治疗的潜在用途的肿瘤疾病。

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来源
《Journal of Cellular Physiology》 |2003年第3期|325-340|共16页
作者
van de Mark K; Chen JS; Steliou KPerrine SPFaller DV;
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作者单位

Cancer Research Center, Boston University School of Medicine, Boston, Massachusetts 02118, USA.;

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正文语种英语
中图分类细胞生物学;
关键词
Cell Line; Tumor cell lines; Cell Cycle ArrestTumor Suppressor ProteinsAntioxidantsCell Cycle CheckpointsCell Cycle ProteinsThioctic AcidApoptosis;

机译：细胞系;肿瘤细胞株细胞周期ArrestTumor抑制ProteinsAntioxidantsCell周期CheckpointsCell ProteinsThioctic循环AcidApoptosis;

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Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines.

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