DNA binding and oxidative DNA damage induced by a quercetin copper(II) complex: potential mechanism of its antitumor properties.
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.
Tan
Jun
J
Bioengineering College, Chongqing University, Chongqing, China. tanjunmail@126.com
Wang
Bochu
B
Zhu
Liancai
L
D000230:Adenocarcinoma / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000188:drug therapy; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D010084:Oxidation-Reduction; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D000077022:Survivin; D014783:Viscosity / Q000187:drug effects
C523706:(Cu(4-methylcoumarin-6,7-dioxactetate)(phenanthroline)2); D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D000077022:Survivin; D004247:DNA; D011794:Quercetin; D053148:Caspase 3