Polyamine Metabolism is Sensitive to Glycolysis Inhibition in Human Neuroblastoma Cells [Metabolism]

January 15th, 2015 by Ruiz–Perez, M. V., Medina, M. A., Urdiales, J. L., Keinanen, T. A., Sanchez–Jimenez, F.

Polyamines are essential for cell proliferation, and their levels are elevated in many human tumours. The oncogene n-myc is known to potentiate polyamine metabolism. Neuroblastoma, the most frequent extra-cranial solid tumour in children, harbours the amplification of n-myc oncogene in 25% of the cases, and it is associated with treatment failure and poor prognosis. We evaluated several metabolic features of the human neuroblastoma cell lines Kelly, IMR-32 and SK-N-SH. We further investigated the effects of glycolysis impairment in polyamine metabolism in these cell lines. A previously unknown linkage between glycolysis impairment and polyamine reduction is unveiled. We show that glycolysis inhibition is able to trigger signalling events leading to the reduction of N-Myc protein levels and a subsequent decrease of both ornithine decarboxylase expression and polyamine levels, accompanied by cell cycle blockade preceding cell death. New anti-tumour strategies could take advantage of the direct relationship between glucose deprivation and PA metabolism impairment leading to cell death and its apparent dependence on n-myc. Combined therapies targeting glucose metabolism and PA synthesis could be effective in the treatment of n-myc-expressing tumours.