Xiao et al.: Oleanolic acid-induced cell death This study mainly focused on the evaluation of cytotoxicity of oleanolic acid on normal human hepatic cells. Normal human hepatic cells were exposed to different concentrations of oleanolic acid and the results demonstrated that oleanolic acid induced cell death in a concentration-and time-dependent manner in LO2 cells. Low concentration of oleanolic acid (40 μM) induced apoptosis. Cleavage of caspase 3/7/9 and decrease of mitochondrial membrane potential was detected in normal human hepatic cells. While high concentration of oleanolic acid (80 μM) caused necrosis without producing cleavage of caspase 3/7/9 or DNA fragmentation. Both flow cytometry and PI staining detected necrotic cells. In addition, both low and high concentrations of oleanolic acid had no effect on the generation of intracellular reactive oxygen species. Present data showed that oleanolic acid could induce apoptosis and necrosis in normal human hepatic cells. Oleanolic acid might be a potential hepatotoxin at high dosage.