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(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.
Michaelis
Martin
M
Institut für Medizinische Virologie, Klinikum der J.W. Goethe Universität, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany.
Cinatl
Jaroslav
J
Anand
Puja
P
Rothweiler
Florian
F
Kotchetkov
Rouslan
R
von Deimling
Andreas
A
Doerr
Hans W
HW
Shogen
Kuslima
K
Cinatl
Jindrich
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D012260:Ribonucleases / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012260:Ribonucleases; D020169:Caspases; C058703:ranpirnase