Knowledge of the mechanism by which arsenic trioxide exerts the anti-tumor effects may help in designing a more effective regimen for therapy. Transcription factor Sox2, a key gene implicated in maintaining the "stemness" of embryonic and adult stem cells, plays an important role in the carcinogenesis and maintenance of glioblastoma. Here, we found that the expression of Sox2 at transcriptional level was decreased during As2O3-induced glioma cell apoptosis. And, the ectopic expression of Sox2 attenuated the apoptotic effect of As2O3 on glioma cell. Furthermore. As2O3 inhibited the self-renewal of glioma stem cells, and efficiently induces the apoptosis of glioma stem cells, at least, partly through down-regulation of Sox2. These data identify a previously unrecognized mechanism of the anti-tumor effects of arsenic trioxide. (C) 2011 Elsevier Inc. All rights reserved.