title: Human glioblastoma ADF cells express tyrosinase, L-tyrosine hydroxylase and melanosomes and are sensitive to L-tyrosine and phenylthiourea.
abstract: Melanocytes and neuroblasts share the property of transforming L-tyrosine through two distinct metabolic pathways leading to melanogenesis and catecholamine synthesis, respectively. While tyrosinase (TYR) activity has been shown to be expressed by neuroblastoma it remains to be established as to whether also glioblastomas cells are endowed with this property. We have addressed this issue using the human continuous glioblastoma cell line ADF. We demonstrated that these cells possess tyrosinase as well as L-tyrosine hydroxylase (TH) activity and synthesize melanosomes. Because the two pathways are potentially cyto-genotoxic due to production of quinones, semiquinones, and reactive oxygen species (ROS), we have also investigated the expression of the peroxisomal proliferators activated receptor alpha (PPARalpha) and nuclear factor-kB (NFkB) transcription factor as well the effect of L-tyrosine concentration on cell survival. We report that L-tyrosine down-regulates PPARalpha expression in ADF cells but not neuroblastoma and that this aminoacid and phenylthiourea (PTU) induces apoptosis in glioblastoma and neuroblastoma.
authors.affiliation: Department of Basic and Applied Biology, University of L'Aquila, Via Vetoio, L'Aquila, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bonfigli
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Zarivi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Colafarina
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cimini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ragnelli
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Aimola
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Natali
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Cerù
authors.forename: Fernanda
authors.initials: F
authors.lastname: Amicarelli
authors.forename: Michele
authors.initials: M
authors.lastname: Miranda
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D005557:Formaldehyde; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D020460:Melanosomes / Q000187:drug effects* / Q000201:enzymology*; D008854:Microscopy, Electron; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000648:ultrastructure; D047493:PPAR alpha / Q000378:metabolism; D010670:Phenylthiourea / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014443:Tyrosine / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D047493:PPAR alpha; D012333:RNA, Messenger; D005557:Formaldehyde; D014443:Tyrosine; D010670:Phenylthiourea; D014446:Tyrosine 3-Monooxygenase; D014442:Monophenol Monooxygenase; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases