Human glioblastoma ADF cells express tyrosinase, L-tyrosine hydroxylase and melanosomes and are sensitive to L-tyrosine and phenylthiourea.
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.
Bonfigli
Antonella
A
Department of Basic and Applied Biology, University of L'Aquila, Via Vetoio, L'Aquila, Italy.
Zarivi
Osvaldo
O
Colafarina
Sabrina
S
Cimini
Anna Maria
AM
Ragnelli
Anna Maria
AM
Aimola
Pierpaolo
P
Natali
Pier Giorgio
PG
Cerù
Maria Paola
MP
Amicarelli
Fernanda
F
Miranda
Michele
M
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*
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