| Abstract Body | Neuroblastoma is a tumour of the sympathetic nervous system and the most occurring extra cranial paediatric tumour. It accounts for 15% of paediatric cancer-related deaths and the survival rate for children with high-risk is less than 50% as half of the affected, develop drug resistance and suffer relapse. Thus, finding effective treatments is highly necessary.
Overexpression of the murine double minute 2, MDM2, gene is common in neuroblastoma and is linked to a poorer prognosis for the patients.
This gene negatively regulates the tumour suppressor transcription factor p53, by ubiquitinating it for proteasomal degradation. Additionally, it can cause oncogenic effects independently of p53; one of the mechanisms is by sequestering the mitochondrial complex I subunit, NDUFS1, leading to enhanced ROS production and cell death. For these reasons, targeting MDM2 and the p53-MDM2 interaction could be a promising treatment for cancers.
In this study we investigated whether Nutlin-3a’s, a p53-MDM2 inhibitor, effect on SH-SY5Y neuroblastoma cells is exerted through the NDUFS1 gene pathway.
Cell viability was evaluated after drug treatment with Nutlin-3a, in combination with Z-VAD-FMK, a pan-caspase inhibitor, and Pifithrin-α, a p53-mediated apoptosis inhibitor, followed by assessment of gene expression of NDUFS1 and associated genes NDUFAF2, NUBPL and ND1.
The results show cytotoxicity effects of Nutlin-3a on the cells with no significant changes of the expression of the genes of interest.
Considering these outcomes, we conclude that the transcriptional regulation of NDUFS1 is not the main mechanism activated in Nutlin-3a treated SH-SY5Y cells.
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