Onconase induces caspase-independent cell death in chemoresistant neuroblastoma cells.

Abstract

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(r)DOX(20)) or by high P-gp expression in combination with mutated p53 (UKF-NB-3(r)VCR(10), 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 naïve and drug-resistant neuroblastoma xenografts was confirmed in animals.

• Authors: Martin Michaelis, Jaroslav Cinatl, Puja Anand, Florian Rothweiler, Rouslan Kotchetkov, Andreas von Deimling, Hans W Doerr, Kuslima Shogen, Jindrich Cinatl Jr
• Journal: Cancer letters (Cancer Lett) Vol. 250 Issue 1 Pg. 107-16 (May 18 2007) ISSN: 0304-3835 [Print] Ireland
• PMID: 17084521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Ribonucleases
• Caspases
• ranpirnase

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (analysis)
• Animals
• Antineoplastic Agents (pharmacology)
• Caspases (metabolism)
• Cell Cycle
• Cell Death
• Cell Survival (drug effects)
• Drug Resistance, Neoplasm
• Female
• Humans
• Mice
• Mice, Nude
• Neuroblastoma (drug therapy, pathology)
• Ribonucleases (pharmacology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays