Effects of arsenic trioxide on the cellular proliferation, apoptosis and differentiation of human neuroblastoma cells

A human neuroblastoma cell line, IMR-32, was used as an in vitro model system to study the effects of arsenic trioxide (As2O3) on aggressive human neuroblastoma. From 0.5 μM, As2O3 exhibited a dose-dependent inhibition of IMR-32 proliferation. At concentrations of 1.5 μM or higher, As2O3 up-regulated caspase 3, leading to cellular apoptosis. However, neurofilament-200 kDa and tyrosine hydroxylase were not up-regulated, implying minimal neuronal differentiation. Concomitantly, TrkA was down-regulated and TrkB up-regulated. Pre-treatment with the protein kinase C (PKC) inhibitor Ro-31-8220 partially blocked As2O3-mediated apoptosis, meaning that As2O3 might signal through PKC activation. The results suggest that As2O3 might be potentially useful in neuroblastoma.