Hou, Ming-HonMing-HonHouWang, Andrew H.-J.Andrew H.-J.Wang2009-08-052018-07-062009-08-052018-07-062005http://ntur.lib.ntu.edu.tw//handle/246246/163358Mith (mithramycin) forms a 2:1 stoichiometry drug-metal complex through the chelation with Fe(II) ion as studied using circular dichroism spectroscopy. The binding affinity between Mith and Fe(II) is much greater than other divalent metal ions, including Mg(II), Zn(II), Co(II), Ni(II) and Mn(II). The [(Mith)2-Fe(II)] complex binds to DNA and induces a conformational change of DNA. Kinetic analysis of surface plasmon resonance studies revealed that the [(Mith)2 -Fe(II)] complex binds to DNA duplex with higher affinity compared with the [(Mith)2-Mg(II)] complex. A molecular model of the Mith-DNA-Metal(II) complex is presented. DNA-break assay showed that the [(Mith)2-Fe(II)] complex was capable of promoting the one-strand cleavage of plasmid DNA in the presence of hydrogen peroxide. Intracellular Fe(II) assays and fluorescence microscopy studies using K562 indicated that this dimer complex maintains its structural integrity and permeates into the inside of K562 cells, respectively. The [(Mith)2-Fe(II)] complex exhibited higher cytotoxicity than the drug alone in some cancer cell lines, probably related to its higher DNA-binding and cleavage activity. Evidences obtained in this study suggest that the biological effects caused by the [(Mith)2 -Fe(II)] complex may be further explored in the future. ? The Author 2005. Published by Oxford University Press. All rights reserved.application/pdf521150 bytesapplication/pdfen-US[SDGs]SDG3[SDGs]SDG6cobalt; double stranded DNA; ferric ion; hydrogen peroxide; magnesium ion; manganese; metal complex; mithramycin; nickel; plasmid DNA; zinc ion; antineoplastic antibiotic; bis(mithromycin)iron(II); divalent cation; DNA; drug derivative; ferrous ion; iron chelating agent; metal; mithramycin; article; binding affinity; binding kinetics; cancer cell culture; cell strain K 562; circular dichroism; complex formation; controlled study; DNA cleavage; DNA strand breakage; drug cytotoxicity; drug DNA interaction; drug structure; fluorescence microscopy; human; human cell; iron chelation; membrane transport; priority journal; surface plasmon resonance; cell membrane permeability; chemical structure; chemistry; conformation; metabolism; nucleotide sequence; plasmid; tumor cell line; Antibiotics, Antineoplastic; Base Sequence; Cations, Divalent; Cell Line, Tumor; Cell Membrane Permeability; Circular Dichroism; DNA; Ferrous Compounds; Humans; Iron Chelating Agents; K562 Cells; Metals; Models, Molecular; Nucleic Acid Conformation; Plasmids; Plicamycin; Surface Plasmon Resonance10.1093/nar/gki276http://ntur.lib.ntu.edu.tw/bitstream/246246/163358/1/25.pdf