Translational inhibitors as potential therapeutic tool of human neuroblastoma through mitochondrial gene expression

Abstract

Neuroblastoma is a solid neuroendocrine tumour and most common type of cancer of infancy. It is a complex heterogeneous disease and many factors such as molecular, cellular and genetic features are involved in its development. Mitochondria play a pivotal role in neuronal cell survival or death. Neurons are highly reliant on aerobic oxidative phosphorylation (OXPHOS) for their energy needs. Defective activities of mitochondrial complexes I, II, III and IV have been identified in many neurological and neurodegenerative diseases. Human mitochondria with its own genetic material meet the needs required for the assembly of subunits of the oxidative phosphorylation (OXPHOS) complexes. A number of translational inhibitors are known that could potentially effect translation of mitochondrial protein synthesis. Among these puromycin, homoharringtonine and cyclohexamide were selected for the present study. The effect of these translational inhibitors on mitochondrial gene expression for the treatment of neuroblastoma are not well established. Therefore, in this study, we have investigated the effects of these translational inhibitors on the expression of human mitochondrial gene expression in SH-SY5Y neuroblastoma cells.

We observed a significant effect on the level of mitochondrial transcripts upon exposure to these translation inhibitors in SH-SY5Y cells, however, the effects on expression of mitochondrial proteins were minimal. This suggests that translational inhibitors might not directly affect the abundance of mitochondrial proteins. Translational inhibitors induce significant effect on mitochondrial gene expression that can be lead to the new-targeted therapy for treating neuroblastoma.