title: Increased resistance of glioma cell lines to extracellular ATP cytotoxicity.
abstract: Glioblastomas are the most common form of primary tumors of the central nervous system (CNS) and despite treatment, patients with these tumors have a very poor prognosis. ATP and other nucleotides and nucleosides are very important signaling molecule in physiological and pathological conditions in the CNS. ATP is degraded very slowly by gliomas when compared to astrocytes, potentially resulting in the accumulation of extracellular ATP around gliomas. Cell lysis caused by excitotoxic death or by tumor resection may liberate intracellular ATP, a known mitotic factor for glioma cells. The aim of this study is to examine the effects on cytotoxicity induced by extracellular ATP in U138-MG human glioma cell line and C6 rat glioma cell line compared to hippocampal organotypic cell cultures. The cytotoxicity of ATP (0.1, 0.5, 5 mM) was measured using propidium iodide and LDH assays. Caspases assay was performed to identify apoptotic cell death. Results showed that the glioma cells present resistance to death induced by ATP when compared with a normal tissue. High ATP concentrations (5 mM) induced cell death after 24 h in organotypic cell cultures but not in glioma cell lines. Our data indicate that ATP released in these situations can induce cell death of the normal tissue surrounding the tumor, potentially opening space to the fast growth and invasion of the tumor.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas de Saúde, UFRGS, Rua Ramiro Barcelos 2600-Anexo, 90.035.003, Porto Alegre, RS, Brazil.
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Morrone
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Horn
authors.forename: Joseli
authors.initials: J
authors.lastname: Stella
authors.forename: Fernando
authors.initials: F
authors.lastname: Spiller
authors.forename: João J F
authors.initials: JJ
authors.lastname: Sarkis
authors.forename: Christianne G
authors.initials: CG
authors.lastname: Salbego
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.forename: Ana Maria O
authors.initials: AM
authors.lastname: Battastini
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D045604:Extracellular Fluid; D005910:Glioma / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009994:Osmolar Concentration; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7
chemical_list: C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; D058910:Purinergic P2 Receptor Agonists; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate