Onconase induces caspase-independent cell death in chemoresistant neuroblastoma cells

The efficacy of Onconase on the growth of a panel of chemosensitive and chemoresistant neuroblastoma cell lines was investigated. Onconase decreased cell viability of chemosensitive (IMR-32, UKF-NB-3) and chemoresistant neuroblastoma cell lines characterised by high expression of P-glycoprotein (P-gp) (UKF-NB-3'DOX20) or by high P-gp expression in combination with mutated p53 (UKF-NB-3'VCR10, Be(2)-C), in a similar manner. Moreover, Onconase caused cell cycle block in G1 phase and induced caspase-independent cell death. Transmission electron microscope investigations suggested that Onconase-induced autophagy contributes to Onconase-induced cell death. Antitumour activity of Onconase against naive and drug-resistant neuroblastoma xenografts was confirmed in animals. (c) 2006 Elsevier Ireland Ltd. All rights reserved.