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

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), H(2)O(2) and O(2)(-) 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 mu M Cu(II) enhanced the necrosis induced by 100 mu M KQ. Treatment of SCM-1 cells with 100 mu M KQ in the presence of 300 mu M Cu(II) increased the generation of H(2)O(2). Taken together, the above finding suggested that KQ cotreatment with Cu(II) produced increased amounts of H(2)O(2), thus enhancing subsequent cell death due to necrosis.