Dihydroartemisinin potentiates the cytotoxic effect of temozolomide in rat C6 glioma cells.

Gliomas are the most common primary brain tumor in adults, but the efficacy of chemotherapy is limited. Artemisinin and its analogs, such as dihydroartemisinin (DHA), can kill cancer cells via generating free radicals. In the present study, we determined whether DHA at low concentrations potentiates the cytotoxic effect of temozolomide in rat glioma C6 cells. We found that the IC50 values of DHA and temozolomide for cell viability were 23.4 and 560 micromol/l, respectively. The cytotoxic effect of temozolomide was enhanced by 177% at a nontoxic DHA concentration (1 micromol/l), and by 321% at a low-toxic DHA concentration (5 micromol/l). DHA substantially increased temozolomide-induced apoptosis and necrosis. The generation of intracellular reactive oxygen species (ROS) was increased by temozolomide combined with DHA at noneffective concentrations of both agents. Edaravone (20 micromol/l), a ROS scavenger, reversed the effects of temozolomide/DHA on both ROS generation and cell viability reduction. These results indicate that DHA at low concentrations potentiates the cytotoxic effects of temozolomide in C6 cells partly via generating ROS, suggesting a beneficial combination for the chemotherapy of gliomas.