Dual blockade of mitogen-activated protein kinases ERK-1 (p42) and ERK-2 (p44) and cyclic AMP response element binding protein (CREB) by neomycin inhibits glioma cell proliferation.
Several growth factors and their receptors are expressed in inappropriately high abundance in gliomas and are further upregulated during the transition from low- to high-grade malignancy. In glioma cells growth factors induce expression of mitogen-activated protein kinase (MAPK) pathways. Here we report that neomycin restrained glioma cell proliferation in vitro by inhibition of p42/44 MAPK and the cyclic AMP element binding protein (CREB)-directed transcription pathways. Since alteration of gene transcription by inhibition of specific transcriptional regulatory proteins has important therapeutic potential, neomycin offers great promise for treating cancer and other diseases associated with a sustained MAPK activity.
Cuevas
Pedro
P
Departamento de Investigación, Hospital Universitario Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain. pedro.cuevas@hrc.es
Diaz-González
Diana
D
Carceller
Fernando
F
Dujovny
Manuel
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D005910:Glioma / Q000378:metabolism; D007150:Immunohistochemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000493:pharmacokinetics*; D051381:Rats; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D011500:Protein Synthesis Inhibitors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D009355:Neomycin