Bhat S H, Azmi A S, Hadi S M
Department of Biochemistry, Faculty of Life Sciences, A.M.U., Aligarh 202002 (U.P.), India.
Toxicol Appl Pharmacol. 2007 Feb 1;218(3):249-55. doi: 10.1016/j.taap.2006.11.022. Epub 2006 Nov 29.
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 in human peripheral lymphocytes. 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 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.
植物源膳食物质含有几类多酚，如黄酮类、姜黄素类、芪类和羟基肉桂酸。它们被认为是天然存在的抗氧化剂，但在过渡金属离子（如铜）存在的情况下，也可作为促氧化剂催化细胞DNA降解。此前我们已表明，芪类白藜芦醇能够动员内源性铜离子，导致细胞DNA发生氧化断裂。在本文中，我们表明咖啡的主要成分之一咖啡酸（一种羟基肉桂酸）也能够导致人外周血淋巴细胞的DNA断裂。用新铜试剂孵育淋巴细胞可抑制DNA降解，证实Cu(I)是DNA裂解反应的中间体。此外，我们还表明咖啡酸在淋巴细胞中产生氧化应激，而活性氧清除剂和新铜试剂可抑制这种氧化应激。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（可能是与染色质结合的铜）的动员以及随之而来的促氧化作用。
