Sensitivity of polyamine metabolism to glucose deprivation is increased in neuroblastoma cells with N-myc amplification

Abstract

Ornithine-derived polyamines are essential for cell proliferation, and their levels are elevated in many human tumors. Neuroblastoma, the most frequent extra-cranial solid tumor in children, harbors amplification of n-myc oncogene (which enhances polyamine metabolism) in 25% of the cases. In the present communication, the relevance of n-myc amplification in several metabolic features of human neuroblastoma cell lines is studied. A previously unknown linkage between glycolysis impairment and polyamine reduction, related to n-myc amplification, is unveiled. Results show that glycolysis inhibition is able to trigger signaling events leading to the reduction of N-Myc protein levels and subsequent decrease of both ornithine decarboxylase expression and polyamine levels, accompanied by cell cycle blockade preceding cell death. Metabolism-targeted therapies are emerging as new approaches for cancer treatment. New anti-tumor strategies could take advantage of the direct relationship between glucose deprivation and PA metabolism impairment leading to cell death described in the present work, and its apparent dependence on n-myc amplification in the case of neuroblastoma. Combined therapies targeting glucose metabolism and polyamine synthesis could be effective in the treatment of n-myc amplified tumors.