Cell death induced by flavonoid glycosides with and without copper

The ability of flavonoid glycosides isolated from several plants to induce DNA breakage was examined using supercoiled plasmid pBR322 DNA by agarose gel electrophoresis in the presence of Cu(II). Among all the compounds, 1, 4, and 6 could cause significant breakages of supercoiled plasmid pBR322 DNA in the presence of Cu(II). Cu(I) was not shown to be an essential intermediate in the process of pBR322 DNA breakage by using the Cu(I)-specific sequestering reagent neocuproine. A decreased cell viability was enhanced in gastric carcinoma SCM-1 cells treating with lower concentrations of 1 and 6 when cotreated with increased concentrations of Cu(II), respectively. Treatments of SCM-1 cells with 500 mu M of 1 in the presence of 300 or 500 mu M of Cu(II) inhibited the Cu(II)-induced apoptosis. Compound 1 (500 mu M) could prevent cell death by inhibiting the 500 mu M Cu(II)-induced apoptosis and necrosis, but did not have any effect on the mitochondrial membrane potential changed by 500 mu M Cu(II). Both compounds 1 and 6 could inhibit the DNA breakages caused by O(2)(center dot-) while 1 also revealed inhibitory effect on xanthine oxidase with an IC(50) value of 22.7 +/- 6.9 mu M. These results indicated that compound 1 with a higher concentration may probably mediate through the suppression of xanthine oxidase activity and reduce reactive oxygen species (ROS) induced by high concentration of Cu(II) (500 mu M) and prevent the following cell death. (c) 2008 Elsevier Ltd. All rights reserved.