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From GC-rich DNA binding to the repression of survivin gene for quercetin nickel (II) complex: implications for cancer therapy

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Abstract

The DNA binding and cleavage properties of quercetin nickel (II) complex have been studied, but little attention has been devoted to the relationship between antitumor activity of this complex and DNA-binding properties. In the present study, we report that quercetin nickel (II) complex showed significant cytotoxicity against three tumor cell lines (HepG2, SMMC7721 and A549). Hoechst33258 and AO/EB staining showed HepG2 cells underwent the typical morphologic changes of apoptosis characterized by nuclear shrinkage, chromatin condensation, or fragmentation after exposure to quercetin nickel (II) complex. We also demonstrate that the levels of survivin and bcl-2 protein expression in HepG2 cells decreased concurrently, and the levels of p53 protein increased significantly after treatment with quercetin nickel (II) complex by immunocytochemistry analysis. The relative activity of caspase-3 and caspase-9 increased significantly after treatment with the complex. Furthermore, fluorescence measurements and molecular modeling were performed to learn that the complex could be preferentially bound to DNA in GC region. These results imply that quercetin nickel (II) complex may intercalate into the GC-rich core promoter region of survivin, down-regulating survivin gene expression and promoting tumor cells apoptosis. So our results suggest that antitumor activity of quercetin nickel (II) complex might be related to its intercalation into DNA and DNA-binding selectivity, and that the complex may be a promising agent for cancer therapy.

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Acknowledgments

This work was financially supported by National Natural Science Foundation of China (No. 20901086), China Postdoctoral Science Foundation funded project (No. 20090450788), and the Fundamental Research Funds for the Central Universities (No. CDJRC10230002).

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Authors and Affiliations

  1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, No. 174, Shapingba Main Street, Chongqing, 400030, China

    Jun Tan, Liancai Zhu & Bochu Wang

  2. Department of Life Science & Chemistry, Chongqing Education College, Chongqing, 400067, China

    Jun Tan

  3. Post-Doctoral Research Center of Mechanics, Mechanical Resource and Environment College, Chongqing University, Chongqing, 400030, China

    Jun Tan

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  1. Jun Tan
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  2. Liancai Zhu
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  3. Bochu Wang
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Correspondence to Jun Tan.

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Tan, J., Zhu, L. & Wang, B. From GC-rich DNA binding to the repression of survivin gene for quercetin nickel (II) complex: implications for cancer therapy. Biometals 23, 1075–1084 (2010). https://doi.org/10.1007/s10534-010-9353-x

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