Pharmacological blockade of group II metabotropic glutamate receptors reduces the growth of glioma cells in vivo

Arcella, A. and Carpinelli, G. and Battaglia, G. and D'Onofrio, M. and Santoro, F. and Ngomba, R. T. and Bruno, V. and Casolini, P. and Giangaspero, F. and Nicoletti, F. (2005) Pharmacological blockade of group II metabotropic glutamate receptors reduces the growth of glioma cells in vivo. Neuro-Oncology, 7 (3). pp. 236-245. ISSN 1522-8517

Full content URL: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC187191...

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Abstract

U87MG human glioma cells in cultures expressed metabotropic glutamate (mGlu) receptors mGlu2 and mGlu3. Addition of the mGlu2/3 receptor antagonist LY341495 to the cultures reduced cell growth, expression of cyclin D1/2, and activation of the MAP kinase and phosphatidylinositol-3-kinase pathways. This is in line with the evidence that activation of mGlu2/3 receptors sustains glioma cell proliferation. U87MG cells were either implanted under the skin (1 × 106 cells/0.5 ml) or infused into the caudate nucleus (0.5 × 106 cells/5 μl) of nude mice. Animals were treated for 28 days with mGlu receptor antagonists by means of subcutaneous osmotic minipumps. Treatments with LY341495 or (2S)-α-ethylglutamate (both infused at a rate of 1 mg/kg per day) reduced the size of tumors growing under the skin. Infusion of LY341495 (10 mg/kg per day) also reduced the growth of brain tumors, as assessed by magnetic resonance imaging analysis carried out every seven days. The effect of drug treatment was particularly evident during the exponential phase of tumor growth, that is, between the third and the fourth week following cell implantation. Immunohistochemical analysis showed that U87MG cells retained the expression of mGlu2/3 receptors when implanted into the brain of nude mice. These data suggest that mGlu2/3 receptor antagonists are of potential use in the experimental treatment of malignant gliomas.

Keywords:2 amino 2 (2 carboxycyclopropyl) 3 (xanthen 9 yl)propionic acid, alpha ethylglutamate, alpha methyl 4 tetrazolylphenylglycine, cyclin D1, cyclin D2, glutamate receptor antagonist, metabotropic receptor 2, metabotropic receptor 3, metabotropic receptor antagonist, mitogen activated protein kinase, phosphatidylinositol 3 kinase, unclassified drug, animal experiment, animal model, antineoplastic activity, article, cancer cell culture, cancer graft, cancer growth, cancer inhibition, caudate nucleus, cell proliferation, controlled study, drug efficacy, enzyme activation, glioma, glioma cell, human, human cell, immunohistochemistry, in vivo study, male, mouse, nonhuman, nuclear magnetic resonance imaging, nude mouse, protein expression, receptor blocking, 1-Phosphatidylinositol 3-Kinase, Amino Acids, Animals, Blotting, Western, Brain Neoplasms, Cell Line, Tumor, Cyclins, Excitatory Amino Acid Antagonists, Humans, Ki-67 Antigen, Magnetic Resonance Imaging, MAP Kinase Signaling System, Mice, Mice, Nude, Receptors, Metabotropic Glutamate, Reverse Transcriptase Polymerase Chain Reaction, Xanthenes
Subjects:B Subjects allied to Medicine > B210 Pharmacology
B Subjects allied to Medicine > B140 Neuroscience
Divisions:College of Science > School of Pharmacy
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ID Code:22163
Deposited On:18 Feb 2016 15:53

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