Solid tumor cell apoptosis induced by arsenic trioxide is related to generation of reactive oxygen species

AIM: To study the effects of As_2O_3 on the growth of human cervical carcinoma cell line, HeLa cells, human pancreatic carcinoma cell line, AsPC-1 cells, and the generation of reactive oxygen species (ROS) in the cells. METHODS: HeLa cells and AsPC-1 cells were treated with various concentrations of As_2O_3. The effects of As_2O_3 on HeLa cells and AsPC-1 cells survival and apoptosis were determined by MTT assay and light microscope, and cellular ROS was also measured by fluorometer. RESULTS: After being treated with 2 μmol/L As_2O_3 for 48 h, the survival of HeLa cells was decreased, a marked apoptosis characteristic was observed in time- and dose-dependent manner. However, the survival of AsPC-1 cells markedly decreased after being treated with even 1μmol/L As_2O_3 for 24 h. When we measured the cellular hydrogen peroxide (H_2O_2) level, we found that the H_2O_2 level in HeLa cells started to rise after being incubated with As_2O_3 for 2 h, and sustained increased, reached the peak of H_2O_2 level at 8 h, then it began to decrease. While the H_2O_2 level in AsPC-1 cells started to rise at 2 h, reached the highest point at 5 h, after which it began to descend. At 12 h, the H_2O_2 level in HeLa cells and AsPC-1 cells were similar to that of the control group. CONCLUSION: The molecular mechanisms underlying As_2O_3 -induced apoptosis in cells derived from the solid tumors may be related to the cellular ROS level.