Kazinol Q from Broussonetia kazinoki Enhances Cell Death Induced by Cu(ll) through Increased Reactive Oxygen Species

Abstract: The ability of the flavan kazinol Q (KQ) to induce DNA breakage in the presence of Cu(II) was examined by agarose gel electrophoresis using supercoiled plasmid DNA. In KQ-mediated DNA breakage reaction, the involvement of reactive oxygen species (ROS), H₂O₂ and O₂ ^- was established by the inhibition of DNA breakage by catalase and revealed DNA breakage by superoxide dismutase (SOD). The cell viability of gastric carcinoma SCM-1 cells treated with various concentrations of KQ was significantly decreased by cotreatment with Cu(II). Treatment of SCM-1 cells with 300 μM Cu(II) enhanced the necrosis induced by 100 μM KQ. Treatment of SCM-1 cells with 100 mM KQ in the presence of 300 mM Cu(II) increased the generation of H₂O₂. Taken together, the above finding suggested that KQ cotreatment with Cu(II) produced increased amounts of H₂O₂, thus enhancing subsequent cell death due to necrosis.