Synergistic effects of multiple treatments, and both DNA and RNA direct bindings on, green tea catechins

Synergistic effects of multiple treatments, and both DNA and RNA direct bindings on, green tea catechins
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DOI:
10.1002/mc.20332
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发表时间:
2007-08-01
影响因子:
4.6
通讯作者:
Fujiki, Hirota
Fujiki, Hirota
中科院分区:
医学2区
文献类型:
--
作者:
Kuzuhara, Takashi;Tanabe, Akitoshi;Fujiki, Hirota

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本文综述了两个主要问题:(1)绿茶儿茶素与多种处理的协同效应;(2)表没食子儿茶素没食子酸酯(EGCG)与DNA和RNA分子的直接结合。日本人整天喝绿茶,因此我们研究了EGCG对细胞的多重处理是否会增强细胞凋亡相关基因的表达,如生长停滞和DNA损伤诱导基因(GADD153)和细胞周期蛋白依赖性激酶抑制基因(p21(Waf1)):结果表明,多种处理协同增强GADD153和p21(Waf1)基因的表达在绿茶饮料预防人类癌症中起着重要作用。我们之前的观察--从儿茶素处理的细胞中提取的核酸是有色的--允许我们推测儿茶素直接与核酸相互作用。表面等离子体共振分析(Biacore)表明,4种儿茶素:EGCG、(-)-表儿茶素没食子酸酯(CG)、(+)-没食子儿茶素没食子酸酯(GCG)和(+)-儿茶素没食子酸酯(CG)能与DNA低聚体结合。冷喷雾电离质谱仪(CSI-MS)分析表明,1~3个EGCG分子与18个单链DNA和RNA结合。此外,一个或两个EGCG分子结合到不同核苷酸长度的双链AG:CT寡聚体上。双链DNA(DsDNA)寡聚体在高温下只以EGCG结合形式存在,而在低温下既有游离态又有结合态,这表明EGCG保护双链DNA寡聚体不会双链熔化成单链DNA。我们认为,在体内,通过多次饮用绿茶饮料,儿茶素在双链DNA和RNA分子中都会积聚,积累的绿茶儿茶素对人类癌症的预防具有重要作用。(C)2007年Wiley-Liss,Inc.
This article reviews two main topics: (1) the synergistic effects of multiple treatments with green tea catechin and (2) the direct binding of (-)-epigallocatechin gallate (EGCG) to both DNA and RNA molecules. Japanese drink green tea throughout the day, so we studied whether multiple treatments of cells with EGCG would enhance the expression of apoptosis-related genes, such as growth arrest and DNA damage-inducible gene (GADD153) and cyclin-dependent kinase inhibitor gene (p21(waf1)): The results suggest that the synergistic enhancement of both GADD153 and p21(waf1) gene expressions by multiple treatments plays a significant role in human cancer prevention with green tea beverage. Our previous observation-that nucleic acids extracted from catechin-treated cells are colored-allowed us to speculate that catechins directly interact with nucleic acids. Surface plasmon resonance assay (Biacore) indicated that four catechins, EGCG, (-)-epicatechin gallate (ECG), (+)-gallocatechin gallate (GCG), and (+)-catechin gallate (CG), bound to DNA oligomers. Cold spray ionization mass spectrometry (CSI-MS) analysis showed that one to three EGCG molecules bound to single-stranded 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to double-stranded AG:CT oligomers of various nucleotide lengths. Double-stranded DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature, whereas at low temperature both the free and bound forms were detected, suggesting that EGCG protects double-stranded DNA oligomers from double-stranded melting into single-stranded DNA. We assume that catechins accumulate in both double-stranded DNA and RNA molecules through multiple administrations of green tea beverage in in vivo, and that the accumulated green tea catechins play a significant role for human cancer prevention. (c) 2007 Wiley-Liss, Inc.