Tan Jun, Wang Bochu, Zhu Liancai
Bioengineering College, Chongqing University, Chongqing, China.
J Biol Inorg Chem. 2009 Jun;14(5):727-39. doi: 10.1007/s00775-009-0486-8. Epub 2009 Mar 4.
The interaction of a quercetin copper(II) complex with DNA was investigated using UV-vis spectra, fluorescence measurement, viscosity measurement, agarose gel electrophoresis, and thiobarbituric acid reactive substances assay. The results indicate that the quercetin copper(II) complex can promote the cleavage of plasmid DNA, producing single and double DNA strand breaks, and intercalate into the stacked base pairs of DNA. Moreover, the complex can induce oxidative DNA damage involving generation of reactive oxygen species such as H(2)O(2) and Cu(I)OOH. In addition, the cytotoxicity experiments carried out with A549 cells confirmed its apoptosis-inducing activity. And we also demonstrate that the levels of survivin protein expression in A549 cells decreased, and that relative activity of caspase-3 increased significantly after treatment with the complex. So our results suggest that the antitumor mechanism of the quercetin copper(II) complex involves not only its oxidative DNA damage with generation of reactive oxygen species but also its specific interaction with DNA.
利用紫外可见光谱、荧光测量、粘度测量、琼脂糖凝胶电泳和硫代巴比妥酸反应物质测定法，研究了槲皮素铜（II）配合物与DNA的相互作用。结果表明，槲皮素铜（II）配合物可促进质粒DNA的切割，产生单链和双链DNA断裂，并插入DNA的堆积碱基对中。此外，该配合物可诱导涉及活性氧如H(2)O(2)和Cu(I)OOH生成的氧化性DNA损伤。此外，用A549细胞进行的细胞毒性实验证实了其诱导凋亡的活性。并且我们还证明，用该配合物处理后，A549细胞中生存素蛋白表达水平降低，而半胱天冬酶-3的相对活性显著增加。因此，我们的结果表明，槲皮素铜（II）配合物的抗肿瘤机制不仅涉及其通过产生活性氧引起的氧化性DNA损伤，还涉及其与DNA的特异性相互作用。
