RT Journal Article
T1 Cannabinoids Induce Glioma Stem-like Cell Differentiation and Inhibit Gliomagenesis
A1 Aguado Sánchez, Tania
A1 Arkaitz Carracedo, 
A1 Boris Julien, 
A1 Velasco Díez, Guillermo
A1 Garry Milman, 
A1 Raphael Mechoulam, 
A1 Luis Alvarez, 
A1 Guzmán Pastor, Manuel
A1 Galve Roperh, Ismael
AB Glioma stem-like cells constitute one of the potential origins of gliomas, and therefore, their elimination is an essential factor for the development of efficient therapeutic strategies. Cannabinoids are known to exert an antitumoral action on gliomas that relies on at least two mechanisms: induction of apoptosis of transformed cells and inhibition of tumor angiogenesis. However, whether cannabinoids target human glioma stem cells and their potential impact in gliomagenesis are unknown. Here, we show that glioma stem-like cells derived from glioblastoma multiforme biopsies and the glioma cell lines U87MG and U373MG express cannabinoid type 1 (CB1) and type 2 (CB2) receptors and other elements of the endocannabinoid system. In gene array experiments, CB receptor activation altered the expression of genes involved in the regulation of stem cell proliferation and differentiation. The cannabinoid agonists HU-210 and JWH-133 promoted glial differentiation in a CB receptor-dependent manner as shown by the increased number of S-100β- and glial fibrillary acidic protein-expressing cells. In parallel, cannabinoids decreased the cell population expressing the neuroepithelial progenitor marker nestin. Moreover, cannabinoid challenge decreased the efficiency of glioma stem-like cells to initiate glioma formation in vivo, a finding that correlated with decreased neurosphere formation and cell proliferation in secondary xenografts. Gliomas derived from cannabinoid-treated cancer stem-like cells were characterized with a panel of neural markers and evidenced a more differentiated phenotype and a concomitant decrease in nestin expression. Overall, our results demonstrate that cannabinoids target glioma stem-like cells, promote their differentiation, and inhibit gliomagenesis, thus giving further support to their potential use in the management of malignant gliomas.
PB Elsevier
SN 0021-9258
YR 2007
FD 2007
LK https://hdl.handle.net/20.500.14352/91097
UL https://hdl.handle.net/20.500.14352/91097
LA eng
NO Aguado, Tania, et al. «Cannabinoids Induce Glioma Stem-like Cell Differentiation and Inhibit Gliomagenesis». Journal of Biological Chemistry, vol. 282, n.o 9, marzo de 2007, pp. 6854-62. https://doi.org/10.1074/jbc.M608900200.
DS Docta Complutense
RD 7 abr 2025