Abstract
Our previous study using human Daoy medulloblastoma cells showed that the promyelocytic leukemia (PML) gene was significantly upregulated (2.5-fold) in cells positive to prominin-1 antigen (CD133), a possible marker for cancer initiating cells. Arsenic trioxide (As2O3) is known to degrade PML protein and has been used for the treatment of patients with acute PML. In the present study, the effect of PML targeting therapy with As2O3 and cytarabine (Ara-C) on Daoy medulloblastoma cell proliferation was investigated. Daoy cells were pretreated with As2O3 for 6 weeks. The As2O3-pretreated Daoy cells were cultured in medium containing Ara-C and cell viability was examined. Next, the As2O3-pretreated Daoy cells were inoculated into the nude mouse brain and the effect of Ara-C on the tumor size was evaluated. A significant increase in chemosensitivity to Ara-C was observed in the As2O3-pretreated Daoy cells in both in vitro and in vivo conditions. PML and CCND1 (cyclin D1) protein expression of Daoy medulloblastoma cells was downregulated by As2O3 treatment. PML has been proposed as a novel therapeutic target to eradicate quiescent leukemia-initiating cells, and PML-expressing CD133-positive cells are similarly a potential therapeutic target of treatment for medulloblastoma.
