Dobesilate diminishes activation of the mitogen-activated protein kinase ERK1/2 in glioma cells.
Fibroblast growth factors (FGFs) and their receptors, regularly expressed at high levels in gliomas, are further upregulated during the transition of the tumor from low- to high-grade malignancy, and are essential for glioma progression. FGFs induce upregulation of the mitogen-activated protein kinase (MAPK) signaling cascade in cultured glioma cells, which suggests that MAPK pathway participates in the FGF-dependent glioma development. Recently, it has been shown that dobesilate, an inhibitor of FGF mitogenic activity, shows antiproliferative and proapoptotic activities in glioma cell cultures. Accordingly, it should be expected this new synthetic FGF inhibitor to affect the activation levels of MAPK. Here we report that immunocytochemical and Western blot data unequivocally show that treatment of cell cultures with dobesilate causes a significant decrease of the intracellular levels of ERK1/2 activation, one of the components of the MAPK signalling cascade. This finding supports an important role for dobesilate in glioma growth, suggesting that dobesilate should be a treatment to be born in mind for glioma management.
Cuevas
P
P
Servicio de Histología, Departamento de Investigación, Hospital Universitario Ramón y Cajal, Ctra. de Colmenar, km. 9.100, E-28034-Madrid-Spain. pedro.cuevas@hrc.es
Díaz-González
Diana
D
García-Martín-Córdova
C
C
Sánchez
I
I
Lozano
Rosa María
RM
Giménez-Gallego
G
G
Dujovny
M
M
D002123:Calcium Dobesilate / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015398:Signal Transduction
D002123:Calcium Dobesilate; D005346:Fibroblast Growth Factors; D048052:Mitogen-Activated Protein Kinase 3