Mechanism for a new antitumor vanadium complex: hydroxyl radical-dependent DNA cleavage by 1,10-phenanthroline-vanadyl complex in the presence of hydrogen peroxide.
Among vanadium complexes which show inhibition of cell growth for human nasopharyngeal carcinoma KB cell, a newly synthesized 1:1 vanadyl-1,10-phenanthroline complex, VO(phen)2+, was found to cleave supercoiled plasmid Col E1 DNA effectively when hydrogen peroxide was added. But VO2+ ion was less effective. Lineweaver-Burk plots of the complex binding to calf thymus DNA indicated that VO(phen)2+ complex has a high affinity to DNA, as supported by CD spectral measurements. To examine the active species for DNA cleavage by the complex, ESR spin trapping was performed and was found that hydroxyl radicals are generated in a pH-dependent manner in the VO(phen)(2+)-H2O2 system, the optimal pH region being 8.5-9.5. In contrast, no optimum pH was observed in VO(2+)-H2O2 system. Thus, the VO(phen)2+ complex is proposed to bind DNA and cleave it when hydrogen peroxide is present.
Sakurai
H
H
Department of Analytical Chemistry, Kyoto Pharmaceutical University, Japan.
Tamura
H
H
Okatani
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003086:Bacteriocin Plasmids / Q000187:drug effects*; D004249:DNA Damage; D004278:DNA, Superhelical / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical; D007624:KB Cells; D007700:Kinetics; D009942:Organometallic Compounds / Q000494:pharmacology*; D010618:Phenanthrolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species
C091442:1,10-phenanthroline-vanadyl complex; D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D009942:Organometallic Compounds; D010618:Phenanthrolines; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide