DNA binding and oxidative DNA damage induced by a quercetin copper(II) complex: potential mechanism of its antitumor properties

Abstract

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.

Spectroscopic, thermogravimetric and biological studies of Na(I), Ni(II) and Zn(II) complexes of quercetin

“…In other study, the same authors showed that quercetin-copper(II) complex promoted the cleavage of plasmid DNA, producing single and double DNA strand breaks, and intercalated into the stacked base pairs of DNA. Moreover, the complex showed pro-oxidative properties and induced oxidative DNA damage involving generation of reactive oxygen species such (H 2 O 2 and CuOOH) [12]. Other study of Tan et al showed that antitumor activity of quercetin zinc(II) complex might be related to its intercalation into DNA [13].…”

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

“…As of today, very few copper complexes have been described that induce apoptosis through the involvement of the Caspase 3 (C3) [16][17]. The mechanism of C3 activation in copper-mediated cell death has not been fully elucidated [18].…”

Importance of Serum Copper and Vascular Endothelial Growth Factor (VEGF-A) Levels in Postmenopausal Bleeding

“…Copper has been shown to influence the bioactivity or production of a number of angiogenic factors including VEGF-A [5,8] and shares some of the pathways utilized by hypoxia to regulate VEGF-A expression [2,5] demonstrated that copper is having anti-tumor activity [9]. Copper is also required in hemoglobin synthesis and in the catalysis of metabolic oxidation [10].…”