Pharmacological blockade of mGlu2/3 metabotropic glutamate receptors reduces cell proliferation in cultured human glioma cells

Mara D'Onofrio, Antonietta Arcella, Valeria Bruno, Richard T. Ngomba, Giuseppe Battaglia, Vincenza Lombari, Giuseppe Ragona, Antonella Calogero, Ferdinando Nicoletti

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Glial cell proliferation in culture is under the control of metabotropic glutamate (mGlu) receptors. We have examined whether this control extends to human glioma cells. Primary cultures were prepared from surgically removed human glioblastomas. RT-PCR combined with western blot analysis showed that most of the cultures (eight out of 11) expressed group-II mGlu receptors. In two selected cultures (MZC-12 and FCN-9), the mGlu2/3 receptor antagonist, LY341495, slowed cell proliferation when applied to the growth medium from the second day after plating. This effect was reversible because linear cell growth was restored after washing out the drug. LY341495 reduced glioma cell proliferation at concentrations lower than 100 nM, which are considered as selective for mGlu2/3 receptors. In addition, its action was mimicked by the putative mGlu2/3 receptor antagonist (2S)-α-ethylglutamate. The anti-proliferative effect of LY341495 was confirmed by measuring [methyl-3H]-thymidine incorporation in cultures arrested in G0 phase of the cell cycle and then stimulated to proliferate by the addition of 10% fetal calf serum or 100 ng/mL of epidermal growth factor (EGF). In cultures treated with EGF, LY341495 was also able to reduce the stimulation of the mitogen-activated protein kinase (MAPK) pathway, as well as the induction of cyclin D1. Both effects, as well as decreased [methyl-3H]-thymidine incorporation, were partially reduced by co-addition of the potent mGlu2/3 receptor agonist, LY379268. We conclude that activation of group-II mGlu receptors supports the growth of human glioma cells in culture and that antagonists of these receptors should be tested for their ability to reduce tumour growth in vivo.

Original languageEnglish
Pages (from-to)1288-1295
Number of pages8
JournalJournal of Neurochemistry
Volume84
Issue number6
DOIs
Publication statusPublished - Mar 2003

Fingerprint

LY 341495
Metabotropic Glutamate Receptors
Cell proliferation
Glioma
Cell Proliferation
Pharmacology
Cell culture
Epidermal Growth Factor
Thymidine
Growth
LY 379268
Cyclin D1
Cell growth
Mitogen-Activated Protein Kinases
Plating
Washing
Cell Cycle Resting Phase
Tumors
Glioblastoma
Chemical activation

Keywords

  • Cyclin D1
  • Glial proliferation
  • Glioma
  • MAP kinase
  • MGlu receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Pharmacological blockade of mGlu2/3 metabotropic glutamate receptors reduces cell proliferation in cultured human glioma cells. / D'Onofrio, Mara; Arcella, Antonietta; Bruno, Valeria; Ngomba, Richard T.; Battaglia, Giuseppe; Lombari, Vincenza; Ragona, Giuseppe; Calogero, Antonella; Nicoletti, Ferdinando.

In: Journal of Neurochemistry, Vol. 84, No. 6, 03.2003, p. 1288-1295.

Research output: Contribution to journalArticle

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AU - Battaglia, Giuseppe

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