Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties

Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes: Involvement of endogenous copper and a putative mechanism for anticancer properties
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DOI:
10.1016/j.taap.2006.11.022
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发表时间:
2007-02-01
影响因子:
3.8
通讯作者:
Hadi, S. M.
Hadi, S. M.
中科院分区:
医学3区
文献类型:
--
作者:
Bhat, S. H.;Azmi, A. S.;Hadi, S. M.

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植物源性膳食材料含有几类多酚,如类黄酮、姜黄素、二苯乙烯和羟基肉桂酸。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,它们也可以作为促氧化剂催化细胞DNA降解。早些时候,我们已经表明,二苯乙烯白藜芦醇能够调动内源性铜离子,导致细胞DNA的氧化断裂。在本文中,我们发现咖啡的主要成分咖啡酸(一种羟基肉桂酸)也能破坏人类外周淋巴细胞的DNA。用新根碱孵育淋巴细胞抑制DNA降解,证实Cu(I)在DNA裂解反应中都是中间体。此外,我们还表明咖啡酸在淋巴细胞中产生氧化应激,这被活性氧清除剂和新桂树碱抑制。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的动员,可能是染色质结合铜,以及随之而来的促氧化作用。(c) 2006爱思唯尔公司版权所有。
Plant-derived dietary material contains several classes of polyphenols Such as flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are recognized as naturally Occurring antioxidants but also act as prooxidants catalyzing cellular DNA degradation in the presence of transition metal ions such as copper. Earlier we have shown that the stilbene resveratrol is able to mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major constituent of coffee, is also capable of DNA breakage ill human peripheral lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA degradation confirming that Cu(I) is all intermediate in the DNA cleavage reaction. Further, we have also shown that caffeic acid generates 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) 2006 Elsevier Inc. All rights reserved.