title: Polyamine metabolism is sensitive to glycolysis inhibition in human neuroblastoma cells.
abstract: Polyamines are essential for cell proliferation, and their levels are elevated in many human tumors. The oncogene n-myc is known to potentiate polyamine metabolism. Neuroblastoma, the most frequent extracranial solid tumor in children, harbors 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 signaling 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-tumor strategies could take advantage of the direct relationship between glucose deprivation and polyamine metabolism impairment, leading to cell death, and its apparent dependence on n-myc. Combined therapies targeting glucose metabolism and polyamine synthesis could be effective in the treatment of n-myc-expressing tumors.
authors.affiliation: From the Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga), 29071 Málaga, Spain, mariaviruiz@uma.es.
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Ruiz-Pérez
authors.affiliation: From the Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga), 29071 Málaga, Spain, Unidad 741, CIBER de Enfermedades Raras (CIBERER), Málaga, Spain, and.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Medina
authors.affiliation: From the Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga), 29071 Málaga, Spain, Unidad 741, CIBER de Enfermedades Raras (CIBERER), Málaga, Spain, and.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Urdiales
authors.affiliation: the School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627 FIN-70211 Kuopio, Finland.
authors.forename: Tuomo A
authors.initials: TA
authors.lastname: Keinänen
authors.affiliation: From the Universidad de Málaga, Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, and IBIMA (Biomedical Research Institute of Málaga), 29071 Málaga, Spain, Unidad 741, CIBER de Enfermedades Raras (CIBERER), Málaga, Spain, and.
authors.forename: Francisca
authors.initials: F
authors.lastname: Sánchez-Jiménez
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003847:Deoxyglucose / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011073:Polyamines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D011073:Polyamines; D016271:Proto-Oncogene Proteins c-myc; D003847:Deoxyglucose
keywords: Cancer Metabolism; Glycolysis; Myc (C-Myc); N-Myc; Neuroblastoma; Polyamine; Polyamines; Tumor Metabolism