Induction of autophagic cell death in malignant glioma cells by arsenic trioxide

T Kanzawa, Y Kondo, H Ito, S Kondo, I Germano - Cancer research, 2003 - AACR
T Kanzawa, Y Kondo, H Ito, S Kondo, I Germano
Cancer research, 2003AACR
Recent clinical data shows that arsenic trioxide (As2O3) causes remission in patients with
acute promyelocytic leukemia and multiple myeloma without severe side effects. Laboratory
data suggest that As2O3 induces apoptosis or cell differentiation of hematopoietic or solid
tumor cells. To date, there has been no study on the effects of As2O3 on glioma cells. In this
study, we investigated the in vitro effect of As2O3 on cell growth inhibition and cell death
mechanisms in human glioma cells. As2O3 significantly inhibited the proliferation of all six of …
Abstract
Recent clinical data shows that arsenic trioxide (As2O3) causes remission in patients with acute promyelocytic leukemia and multiple myeloma without severe side effects. Laboratory data suggest that As2O3 induces apoptosis or cell differentiation of hematopoietic or solid tumor cells. To date, there has been no study on the effects of As2O3 on glioma cells. In this study, we investigated the in vitro effect of As2O3 on cell growth inhibition and cell death mechanisms in human glioma cells. As2O3 significantly inhibited the proliferation of all six of the glioma cell lines (U373, U87, U251, GB1, A-172, and T98G) tested in this study in a dose-dependent manner. The IC50 of As2O3 for all of the tumor cell lines was <2 μm. Previous studies have shown that this is a clinically safe concentration. Treatment with 2 μm As2O3 induced G2/M arrest in all of the glioma cell lines. Autophagy (programmed cell death type II), but not apoptosis (programmed cell death type I), was detected by electron microscopy in U-373-MG cells treated with 2 μm As2O3. Caspase inhibitors did not halt As2O3-induced cell death. Furthermore, combination of As2O3 with bafilomycin A1 autophagy inhibitor enhanced the antitumor effect of As2O3 through induction of apoptosis. These findings suggest that As2O3 at a clinically safe concentration may be an effective chemotherapeutic agent for malignant gliomas.
AACR