Hanif Sarmad, Shamim Uzma, Ullah M F, Azmi Asfar S, Bhat Showket H, Hadi S M
Department of Biochemistry, Faculty of Life Sciences, AMU, Aligarh 202002, UP, India.
Toxicology. 2008 Jul 10;249(1):19-25. doi: 10.1016/j.tox.2008.03.024. Epub 2008 Apr 9.
Epidemiological and experimental evidence exists to suggest that pomegranate and its juice possess chemopreventive and anticancer properties. The anthocyanidin delphinidin is a major polyphenol present in pomegranates and has been shown to be responsible for these effects. Plant polyphenols are recognized as naturally occurring antioxidants but also catalyze oxidative DNA degradation of cellular DNA either alone or in the presence of transition metal ions such as copper. In this paper we show that similar to various other classes of polyphenols, delphinidin is also capable of causing oxidative degradation of cellular DNA. Lymphocytes were exposed to various concentrations of delphinidin (10, 20, 50 microM) for 1h and the DNA breakage was assessed using single cell alkaline gel electrophoresis (Comet assay). Inhibition of DNA breakage by several scavengers of reactive oxygen species (ROS) indicated that it is caused by the formation of ROS. Incubation of lymphocytes with neocuproine (a cell membrane permeable Cu(I) chelator) inhibited DNA degradation in intact lymphocytes in a dose dependent manner. Bathocuproine, which is unable to permeate through the cell membrane, did not cause such inhibition. We have further shown that delphinidin is able to degrade DNA in cell nuclei and that such DNA degradation is also inhibited by neocuproine suggesting that nuclear copper is mobilized in this reaction. These results indicate that the generation of ROS possibly occurs through mobilization of endogenous copper ions. The results are in support of our hypothesis that the prooxidant activity of plant polyphenols may be an important mechanism for their anticancer properties.
流行病学和实验证据表明，石榴及其汁液具有化学预防和抗癌特性。花青素飞燕草色素是石榴中存在的一种主要多酚，已证明它是造成这些效应的原因。植物多酚被认为是天然存在的抗氧化剂，但也能单独或在过渡金属离子（如铜）存在的情况下催化细胞DNA的氧化降解。在本文中，我们表明，与其他各类多酚类似，飞燕草色素也能够导致细胞DNA的氧化降解。将淋巴细胞暴露于不同浓度的飞燕草色素（10、20、50微摩尔）中1小时，使用单细胞碱性凝胶电泳（彗星试验）评估DNA断裂情况。几种活性氧（ROS）清除剂对DNA断裂的抑制表明，这是由ROS的形成引起的。用新铜试剂（一种细胞膜可渗透的Cu(I)螯合剂）孵育淋巴细胞，以剂量依赖的方式抑制了完整淋巴细胞中的DNA降解。不能透过细胞膜的bathocuproine没有引起这种抑制作用。我们进一步表明，飞燕草色素能够降解细胞核中的DNA，并且这种DNA降解也受到新铜试剂的抑制，这表明在该反应中细胞核中的铜被动员起来。这些结果表明，ROS的产生可能是通过内源性铜离子的动员发生的。这些结果支持了我们的假设，即植物多酚的促氧化活性可能是其抗癌特性的一个重要机制。
