Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: A putative mechanism for anticancer properties
Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: A putative mechanism for anticancer properties
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DOI：
10.1016/j.febslet.2005.12.059
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发表时间：
2006-01-23
期刊：
影响因子：
3.5
通讯作者：
Hadi, SM
中科院分区：
文献类型：
--
作者：
Ami, AS;Bhat, SH;Hadi, SM
植物多酚是人类饮食的重要组成部分，其中许多被认为具有化学预防和治疗癌症的特性。它们被认为是天然存在的抗氧化剂，但在铜等过渡金属离子存在的情况下，它们也可作为催化 DNA 降解的促氧化剂。使用人外周淋巴细胞和彗星实验，我们之前已经证实白藜芦醇-Cu(II)确实能够引起细胞中的DNA降解。在本文中，我们证明单独的多酚（在不添加铜的情况下）也能够引起细胞中的 DNA 断裂。将淋巴细胞与新铜氨酸一起孵育可抑制 DNA 降解，证实 Cu(I) 是 DNA 裂解反应中的中间体。此外，我们还表明多酚会在淋巴细胞中产生氧化应激，而氧化应激可被活性氧清除剂和新铜灵抑制。这些结果进一步支持了我们的假设，即植物多酚的抗癌机制涉及内源性铜（可能是染色质结合铜）的动员，以及随后的促氧化作用。 (c) 2005 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Plant polyphenols are important components of human diet and a number of them are considered to possess chemopreventive and therapeutic properties against cancer. They are recognized as naturally occurring antioxidants but also act as prooxidants catalyzing DNA degradation in the presence of transition metal ions such as copper. Using human peripheral lymphocytes and Comet assay we have previously confirmed that resveratrol-Cu(II) is indeed capable of causing DNA degradation in cells. In this paper we show that the polyphenols alone (in the absence of added copper) are also capable of causing DNA breakage in cells. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is an intermediate in the DNA cleavage reaction. Further, we have also shown that polyphenols generate oxidative stress in lymphocytes which is inhibited by scavengers of reactive oxygen species and neocuproine. These results are in further support of our hypothesis that anticancer mechanism of plant polyphenols involves mobilization of endogenous copper, possibly chromatin bound copper, and the consequent prooxidant action. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.