Arsenic trioxide inhibits the growth of human glioma stem cells through activating the JNK pathway

Abstract

Malignant gliomas are the most common and aggressive primary brain tumor. A major barrier to the treatment of glioma is the drug resistance. The existence of glioma stem cells may be responsible for drug resistance. Recent clinical data show that arsenic trioxide (As2O3) causes remission in patients with acute promyelocytic leukemia without severe side effects. However, it is still unknown that whether As2O3 could inhibit the growth of glioma stem cells. Glioma stem cells are also called glioma stem/progenitor cells (GSPCs). The GSPCs are a population of cells capable of extensive self-renewal, differentiation into multiple lineages, initiated the original tumor in immunodeficient mice and often co-expressed differentiation surface marker with the stem/progenitor cell marker nestin. In this study, we cultivated GSPCs, which were established from the excised tumor tissue of a patient, and showed that As2O3 could inhibit the proliferation of GSPCs. Treatment of GSPCs for 24 h, 48 h and 72 h with As2O3 induced cell death in a dose- and timedependent manner. Subsequently, we demonstrated that the As2O3-induced GSPCs death was due to cell cycle arrest at the G0/G1 transition and was associated with activation of c-jun N-terminal kinase (JNK) pathway. The findings underscore the potential of As2O3 to inhibit the proliferation of GSPCs through the JNK pathway and suggest its application to the effective therapy for patients with glioma.