Aim: To characterize neurotoxicity induced by oxaliplatin, bortezomib, and epothilone-B as well as protection against their neurotoxicity using an in vitro model. Materials and Methods: Neurotoxicity was evaluated using the neurite outgrowth method in PC12 rat pheochromocytoma cells differentiated towards a mature neuronal phenotype, while neuroprotection was explored by simultaneous exposure to 0.5 mM amifostine. The potential markers of neuronal differentiation, cyclin-B2 (Ccnb2) and baculoviral inhibitor of apoptosis repeat-containing 5 (Birc5), were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: Bortezomib, epothilone-B, and oxaliplatin reduced neurite length to 68%, 78% and 66%, respectively (p<0.05). The percentage of neurite-forming-cells (discriminating neurotoxicity from general cytotoxicity) decreased from 70% (control) to 55% (bortezomib), 46% (epothilone-B), and 51% (oxaliplatin). Amifostine was neuroprotective against oxaliplatin-induced neurotoxicity, increasing both neurite length and neurite-forming-cells. Quantitative-RT-PCR showed a 2.7-fold decrease in Ccnb2 expression in differentiated PC12 vs. undifferentiated cells. Conclusion: Oxaliplatin, bortezomib, and epothilone-B are neurotoxic in the PC12 model. Amifostine has a neuroprotective effect only against oxaliplatin-induced neurotoxicity, suggesting that these compounds have different mechanisms of neurotoxicity

Ceresa, C., Avan, A., Giovannetti, E., Geldof, A., Avan, A., Cavaletti, G., et al. (2014). Characterization of and protection from neurotoxicity induced by oxaliplatin, bortezomib and epothilone-B. ANTICANCER RESEARCH, 34(1B), 517-523.

Characterization of and protection from neurotoxicity induced by oxaliplatin, bortezomib and epothilone-B

CERESA, CECILIA;CAVALETTI, GUIDO ANGELO;
2014

Abstract

Aim: To characterize neurotoxicity induced by oxaliplatin, bortezomib, and epothilone-B as well as protection against their neurotoxicity using an in vitro model. Materials and Methods: Neurotoxicity was evaluated using the neurite outgrowth method in PC12 rat pheochromocytoma cells differentiated towards a mature neuronal phenotype, while neuroprotection was explored by simultaneous exposure to 0.5 mM amifostine. The potential markers of neuronal differentiation, cyclin-B2 (Ccnb2) and baculoviral inhibitor of apoptosis repeat-containing 5 (Birc5), were evaluated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: Bortezomib, epothilone-B, and oxaliplatin reduced neurite length to 68%, 78% and 66%, respectively (p<0.05). The percentage of neurite-forming-cells (discriminating neurotoxicity from general cytotoxicity) decreased from 70% (control) to 55% (bortezomib), 46% (epothilone-B), and 51% (oxaliplatin). Amifostine was neuroprotective against oxaliplatin-induced neurotoxicity, increasing both neurite length and neurite-forming-cells. Quantitative-RT-PCR showed a 2.7-fold decrease in Ccnb2 expression in differentiated PC12 vs. undifferentiated cells. Conclusion: Oxaliplatin, bortezomib, and epothilone-B are neurotoxic in the PC12 model. Amifostine has a neuroprotective effect only against oxaliplatin-induced neurotoxicity, suggesting that these compounds have different mechanisms of neurotoxicity
Articolo in rivista - Articolo scientifico
cyclin-B2; PC12 model; amifostine neuroprotection; Neurotoxicity; oxaliplatin
English
2014
34
1B
517
523
none
Ceresa, C., Avan, A., Giovannetti, E., Geldof, A., Avan, A., Cavaletti, G., et al. (2014). Characterization of and protection from neurotoxicity induced by oxaliplatin, bortezomib and epothilone-B. ANTICANCER RESEARCH, 34(1B), 517-523.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/51251
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