Figure 1.

General representation of the signaling pathways involved in the antagonism of both ionotropic and metabotropic glutamate receptors in anti-cancer mediated effects. Selective metabotropic glutamate receptor 1 (mGluR1) antagonist JNJ1659685 elicited its anti-cancer activity, by decreasing cell proliferation, through the inhibition of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, and by increasing cell differentiation through the activation of the transcription factors small mother against decapentaplegic transcription factor (Smad) 1/5/8. LY 341495, an mGluR 2/3 selective antagonist, blocks the activation of both the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)1/2 cascade and the Akt/mammalian target of rapamycin protein (mTOR) pathway, resulting in arrest of the cell cycle and an increase in apoptosis. Talampanel, a selective negative allosteric α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) modulator, inhibits the rise of intracellular calcium concentration, and inhibits both ERK1/2 and Akt phosphorylation, slowing down the cell proliferation, and increasing cellular stiffness through the activation of focal adhesion kinase (FAK) protein. The N-methyl-d-aspartate (NMDA) antagonists, MP1 and MP2, two memantine derivative compounds, exert their antiproliferative activity by modulating Beclin-1 binding protein, which increases the autophagic processes of glioblastoma cell line.