Increased resistance of glioma cell lines to extracellular ATP cytotoxicity

• Published in: Journal of neuro-oncology 2005, Vol.71 (2), p.135-140
• Main Authors: MORRONE, Fernanda B, HORN, Ana Paula, STELLA, Joseli, SPILLER, Fernando, SARKIS, Joao J. F, SALBEGO, Christianne G, LENZ, Guido, BATTASTINI, Ana Maria O
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - administration & dosage; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Antineoplastic agents; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Cells, Cultured; Chemotherapy; Development. Senescence. Regeneration. Transplantation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Extracellular Fluid; Fundamental and applied biological sciences. Psychology; Glioma - pathology; Glioma - physiopathology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Humans; Male; Medical sciences; Neurology; Neurons - drug effects; Neurons - physiology; Osmolar Concentration; Pharmacology. Drug treatments; Purinergic P2 Receptor Agonists; Rats; Rats, Wistar; Receptors, Purinergic P2X7; Vertebrates: nervous system and sense organs
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-004-1383-1

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.