Arsenic trioxide induces apoptosis in neuroblastoma cell lines through the activation of caspase 3 in vitro

Arsenic trioxide (As₂O₃) induces clinical remission in acute promyelocytic leukemia, even in all-trans retinoic acid-refractory cases, with minimal toxicity at low (1-2 μM) concentration. We exposed various neuroblastoma cell lines to As₂O₃ at a concentration of 2 μM: as a result, seven of 10 neuroblastoma cell lines underwent apoptosis characterized by morphological changes and nucleosomal DNA fragmentation. As₂O₃-induced apoptosis in neuroblastoma cells was shown to occur through the activation of caspase 3, as judged from Western blot analysis and apoptosis inhibition assay. It seemed that the sensitivity of neuroblastoma cells to As₂O₃ was inversely proportional to their intracellular level of reduced glutathione. Taken together these results indicate that As₂O₃ would be a candidate as a therapeutic agent for treatment of neuroblastoma, which is a solid tumor, not only by systemic therapy but also by local therapy. Copyright (C) 1999 Federation of European Biochemical Societies.