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人类癌症干细胞是使用(-)-表没食子儿茶素没食子酸酯进行癌症预防的靶点。

Human cancer stem cells are a target for cancer prevention using (-)-epigallocatechin gallate.

作者信息

Fujiki Hirota, Sueoka Eisaburo, Rawangkan Anchalee, Suganuma Masami

机构信息

Faculty of Medicine, Saga University, Nabeshima, Saga, 849-8501, Japan.

Graduate School of Science and Engineering, Saitama University, Saitama, 338-8570, Japan.

出版信息

J Cancer Res Clin Oncol. 2017 Dec;143(12):2401-2412. doi: 10.1007/s00432-017-2515-2. Epub 2017 Sep 23.

Abstract

PURPOSE

Our previous experiments show that the main constituent of green-tea catechins, (-)-epigallocatechin gallate (EGCG), completely prevents tumor promotion on mouse skin initiated with 7,12-dimethylbenz(a)anthracene followed by okadaic acid and that EGCG and green tea extract prevent cancer development in a wide range of target organs in rodents. Therefore, we focused our attention on human cancer stem cells (CSCs) as targets of cancer prevention and treatment with EGCG.

METHODS

The numerous reports concerning anticancer activity of EGCG against human CSCs enriched from cancer cell lines were gathered from a search of PubMed, and we hope our review of the literatures will provide a broad selection for the effects of EGCG on various human CSCs.

RESULTS

Based on our theoretical study, we discuss the findings as follows: (1) Compared with the parental cells, human CSCs express increased levels of the stemness markers Nanog, Oct4, Sox2, CD44, CD133, as well as the EMT markers, Twist, Snail, vimentin, and also aldehyde dehydrogenase. They showed decreased levels of E-cadherin and cyclin D1. (2) EGCG inhibits the transcription and translation of genes encoding stemness markers, indicating that EGCG generally inhibits the self-renewal of CSCs. (3) EGCG inhibits the expression of the epithelial-mesenchymal transition phenotypes of human CSCs. (4) The inhibition of EGCG of the stemness of CSCs was weaker compared with parental cells. (5) The weak inhibitory activity of EGCG increased synergistically in combination with anticancer drugs.

CONCLUSIONS

Green tea prevents human cancer, and the combination of EGCG and anticancer drugs confers cancer treatment with tissue-agnostic efficacy.

摘要

目的

我们之前的实验表明,绿茶儿茶素的主要成分,(-)-表没食子儿茶素没食子酸酯(EGCG),能完全阻止用7,12-二甲基苯并(a)蒽引发、随后用冈田酸处理的小鼠皮肤肿瘤促进作用,并且EGCG和绿茶提取物可预防啮齿动物多种靶器官中的癌症发展。因此,我们将注意力集中在人类癌症干细胞(CSCs)上,将其作为EGCG预防和治疗癌症的靶点。

方法

通过检索PubMed收集了众多关于EGCG对从癌细胞系富集的人类CSCs抗癌活性的报道,我们希望对这些文献的综述能为EGCG对各种人类CSCs的作用提供广泛的选择。

结果

基于我们的理论研究,我们对研究结果进行如下讨论:(1)与亲代细胞相比,人类CSCs表达干性标志物Nanog、Oct4、Sox2、CD44、CD133以及上皮-间质转化(EMT)标志物Twist、Snail、波形蛋白的水平增加,同时醛脱氢酶水平也增加。它们的E-钙黏蛋白和细胞周期蛋白D1水平降低。(2)EGCG抑制编码干性标志物的基因的转录和翻译,表明EGCG通常抑制CSCs的自我更新。(3)EGCG抑制人类CSCs上皮-间质转化表型的表达。(4)与亲代细胞相比,EGCG对CSCs干性的抑制作用较弱。(5)EGCG的弱抑制活性与抗癌药物联合使用时协同增强。

结论

绿茶可预防人类癌症,EGCG与抗癌药物联合使用可赋予癌症治疗组织非特异性疗效。

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