RT Journal Article
T1 Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide
A1 López-Valero, Israel
A1 Saiz-Ladera, Cristina
A1 Torres, Sofía
A1 Hernández-Tiedra, Sonia
A1 García-Taboada, Elena
A1 Rodríguez-Fornés, Fátima
A1 Barba, Marina
A1 Dávila, David
A1 Salvador-Tormo, Nélida
A1 Guzmán Pastor, Manuel
A1 Sepúlveda, Juan Manuel
A1 Sánchez-Gómez, Pilar
A1 Lorente Pérez, María Del Mar
A1 Velasco Díez, Guillermo
AB Glioblastoma multiforme (GBM) is the most frequent and aggressive type of brain tumor due, at least in part, to its poor response to current anticancer treatments. These features could be explained, at least partially, by the presence within the tumor mass of a small population of cells termed Glioma Initiating Cells (GICs) that has been proposed to be responsible for the relapses occurring in this disease. Thus, the development of novel therapeutic approaches (and specifically those targeting the population of GICs) is urgently needed to improve the survival of the patients suffering this devastating disease. Previous observations by our group and others have shown that Δ9-Tetrahydrocannabinol (THC, the main active ingredient of marijuana) and other cannabinoids including cannabidiol (CBD) exert antitumoral actions in several animal models of cancer, including gliomas. We also found that the administration of THC (or of THC + CBD at a 1:1 ratio) in combination with temozolomide (TMZ), the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts. In this work we investigated the effect of the combination of TMZ and THC:CBD mixtures containing different ratios of the two cannabinoids in preclinical glioma models, including those derived from GICs. Our findings show that TMZ + THC:CBD combinations containing a higher proportion of CDB (but not TMZ + CBD alone) produce a similar antitumoral effect as the administration of TMZ together with THC and CBD at a 1:1 ratio in xenografts generated with glioma cell lines. In addition, we also found that the administration of TMZ + THC:CBD at a 1:1 ratio reduced the growth of orthotopic xenografts generated with GICs derived from GBM patients and enhanced the survival of the animals bearing these intracranial xenografts. Remarkably, the antitumoral effect observed in GICs-derived xenografts was stronger when TMZ was administered together with cannabinoid combinations containing a higher proportion of CBD. These findings support the notion that the administration of TMZ together with THC:CBD combinations – and specifically those containing a higher proportion of CBD – may be therapeutically explored to target the population of GICs in GBM.
PB Elsevier
SN 0006-2952
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/101057
UL https://hdl.handle.net/20.500.14352/101057
LA eng
NO López-Valero, Israel, et al. «Targeting Glioma Initiating Cells with A Combined Therapy of Cannabinoids and Temozolomide». Biochemical Pharmacology, vol. 157, noviembre de 2018, pp. 266-74. https://doi.org/10.1016/j.bcp.2018.09.007.
NO AcknowledgementsThis work has been funded by the PI15/00339 grant, integrated into the State Plan for R & D + I2013-2016 and funded by the Instituto de Salud Carlos III (ISCIII) (Spain) and the European Regional Development Fund (ERDF) and by grants from Spanish Ministry of Economy and Competitiveness (MINECO)/ISCIII and ERDF (PS09/01401; PI12/02248,to GV), GW Pharma Ltd. (UK), Comunidad de Madrid (Spain) (S2011/BMD-2308 to MG), Fundación Mutua Madrileña (Spain) (AP101042012 to GV), Fundació La Marató de TV3 (Spain) (201334031 to GV), Voices Against Brain Cancer (US), and donations by The Medical Cannabis Bike Tour Foundation (The Netherlands) and Jeff Ditchfield. Israel López-Valero was supported by a predoctoral P-FIS contract from Instituto de Salud Carlos III (ISCIII) and Cristina Sáiz was supported by a “Juan de la Cierva formación” contract of the Spanish Ministry of Economy and Competitiveness.
NO Instituto de Salud Carlos III
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Pharma Ltd. (UK)
NO Comunidad de Madrid
NO Fundación Mutua Madrileña
NO Fundació La Marató de TV3
NO Voices Against Brain Cancer (US)
NO The Medical Cannabis Bike Tour Foundation (Netherlands)
DS Docta Complutense
RD 29 abr 2025