RT Journal Article
T1 Optimization of a preclinical therapy of cannabinoids in combination with temozolomide against glioma
A1 López-Valero, Israel
A1 Torres, Sofía
A1 Salazar Roa, María
A1 García-Taboada, Elena
A1 Hernández-Tiedra, Sonia
A1 Guzmán Pastor, Manuel
A1 Sepúlveda-Sánchez, Juan Manuel
A1 Lorente Pérez, María Del Mar
A1 Velasco Díez, Guillermo
AB Glioblastoma multiforme (GBM) is the most frequent and aggressive form of brain cancer. These features are explained at least in part by the high resistance exhibited by these tumors to current anticancer therapies. Thus, the development of novel therapeutic approaches is urgently needed to improve the survival of the patients suffering this devastating disease. Δ9-Tetrahydrocannabinol (THC, the major active ingredient of marijuana), and other cannabinoids have been shown to exert antitumoral actions in animal models of cancer, including glioma. The mechanism of these anticancer actions relies, at least in part, on the ability of these compounds to stimulate autophagy-mediated apoptosis in tumor cells. Previous observations from our group demonstrated that local administration of THC (or of THC + CBD at a 1:1 ratio, a mixture that resembles the composition of the cannabinoid-based medicine Sativex®) in combination with Temozolomide, the benchmark agent for the treatment of GBM, synergistically reduces the growth of glioma xenografts. With the aim of optimizing the possible clinical utilization of cannabinoids in anti-GBM therapies, in this work we explored the anticancer efficacy of the systemic administration of cannabinoids in combination with TMZ in preclinical models of glioma. Our results show that oral administration of Sativex-like extracts (containing THC and CBD at a 1:1 ratio) in combination with TMZ produces a strong antitumoral effect in both subcutaneous and intracranial glioma cell-derived tumor xenografts. In contrast, combined administration of Sativex-like and BCNU (another alkylating agent used for the treatment of GBM which share structural similarities with the TMZ) did not show a stronger effect than individual treatments. Altogether, our findings support the notion that the combined administration of TMZ and oral cannabinoids could be therapeutically exploited for the management of GBM.
PB Elsevier
SN 0006-2952
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/98005
UL https://hdl.handle.net/20.500.14352/98005
LA eng
NO López-Valero, Israel, et al. «Optimization of a Preclinical Therapy of Cannabinoids in Combination with Temozolomide against Glioma». Biochemical Pharmacology, vol. 157, noviembre de 2018, pp. 275-84. https://doi.org/10.1016/j.bcp.2018.08.023.
NO AcknowledgementsThis work has been funded by the PI15/00339 grant, integrated into the State Plan for R & D + I2013-2016 (Spain) 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 (AP101042012 to GV) (Spain), Fundació La Marató de TV3 (201334031 to GV)(Spain), Israel López-Valero was supported by a predoctoral P-FIS contract from Instituto de Salud Carlos III (ISCIII). Cannabinoid-related work in G Velasco’s laboratory is also funded by a grant from Voices Against Brain Cancer (USA) and donations by The Medical Cannabis Bike Tour Foundation (The Netherlands) and Jeff Ditchfield.
NO The Medical Cannabis Bike Tour Foundation (The Netherlands)
NO Comunidad de Madrid
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Fundación Mutua Madrileña
NO Fundació La Marató de TV3
NO GW Pharma Ltd (UK)
NO Voices Against Brain Cancer (USA)
DS Docta Complutense
RD 12 abr 2025