title: From GC-rich DNA binding to the repression of survivin gene for quercetin nickel (II) complex: implications for cancer therapy.
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.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, No. 174, Shapingba Main Street, Chongqing, 400030, China. tanjunmail@126.com
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.forename: Liancai
authors.initials: L
authors.lastname: Zhu
authors.forename: Bochu
authors.initials: B
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation; D020862:GC Rich Sequence / Q000502:physiology; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D056831:Coordination Complexes; D004273:DNA, Neoplasm; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009942:Organometallic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D011794:Quercetin