Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells
Green tea constituent (-)-epigallocatechin-3-gallate inhibits topoisomerase I activity in human colon carcinoma cells
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DOI：
10.1006/bbrc.2001.5736
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发表时间：
2001-10-19
影响因子：
3.1
通讯作者：
Mukhtar, H
中科院分区：
文献类型：
--
作者：
Berger, SJ;Gupta, S;Mukhtar, H
DNA拓扑异构酶I和II对于细胞生存至关重要，并在DNA代谢和结构中发挥关键作用。拓扑异构酶抑制剂构成了一个新的抗肿瘤药物家族，在人类恶性肿瘤中具有临床活性。由于对正常细胞的严重毒性作用，这些药物的临床使用受到限制。因此，需要开发新的、无毒的拓扑异构酶抑制剂，其具有保护正常细胞的能力。最近的研究表明，绿色茶及其主要多酚成分表没食子儿茶素-3-没食子酸酯（EGCG）对癌细胞而不是正常细胞产生生长抑制反应。基于EGCG诱导DNA损伤、细胞周期阻滞和凋亡的知识，我们考虑了拓扑异构酶参与EGCG抗增殖反应的可能性。在这里，我们第一次表明，表没食子儿茶素没食子酸酯抑制拓扑异构酶I，但不拓扑异构酶II在几个人结肠癌细胞系。基于这项研究，它是诱人的建议，结合表没食子儿茶素没食子酸酯与其他传统的拓扑异构酶抑制剂可能是一种改进的策略，用于治疗结肠癌。表没食子儿茶素没食子酸酯作为化疗剂的可能作用需要研究。(C)北京：科学出版社.
DNA topoisomerases I and II are essential for cell survival and play critical roles in DNA metabolism and structure. Inhibitors of topoisomerase constitute a novel family of antitumor agents with demonstrated clinical activity in human malignancies. The clinical use of these agents is limited due to severe toxic effects on normal cells. Therefore, there is a need to develop novel, nontoxic topoisomerase inhibitors that have the ability to spare normal cells. Recent studies have shown that green tea and its major polyphenolic constituent, epigallocatechin-3-gallate (EGCG), impart growth inhibitory responses to cancer cells but not to normal cells. Based on the knowledge that EGCG induces DNA damage, cell cycle arrest, and apoptosis, we considered the possibility of the involvement of topoisomerase in the antiproliferative response of EGCG. Here, for the first time, we show that EGCG inhibits topoisomerase I, but not topoisomerase II in several human colon carcinoma cell lines. Based on this study it is tempting to suggest that combination of EGCG with other conventional topoisomerase inhibitors could be an improved strategy for treatment of colon cancer. The possible role of EGCG as a chemotherapeutic agent needs to be investigated. (C) 2001 Academic Press.