2024-03-29T14:51:05Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/78942023-02-01T08:28:12Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2109com_20.500.12105_2052col_20.500.12105_16969col_20.500.12105_2110
Repisalud
author
López-Valero, Israel
author
Saiz-Ladera, Cristina
author
Torres, Sofía
author
Hernández-Tiedra, Sonia
author
García-Taboada, Elena
author
Rodríguez-Fornés, Fátima
author
Barba, Marina
author
Dávila, David
author
Salvador-Tormo, Nélida
author
Guzmán, Manuel
author
Sepúlveda, Juan M
author
Sánchez-Gómez, Pilar
author
Lorente, Mar
author
Velasco, Guillermo
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación Mutua Madrileña
funder
Ministerio de Economía y Competitividad (España)
funder
GW Pharma Ltd. (UK)
funder
Comunidad de Madrid (España)
funder
Fundación La Marató TV3
funder
Voices Against Brain Cancer (US)
funder
The Medical Cannabis Bike Tour Foundation (The Netherlands)
2019-07-11T10:18:38Z
2019-07-11T10:18:38Z
2018
Biochemical Pharmacology Volume 157, November 2018, Pages 266-274
00062952
http://hdl.handle.net/20.500.12105/7894
30195736
10.1016/j.bcp.2018.09.007
1873-2968
Biochemical Pharmacology
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.
eng
Cannabinoids
Combinational therapies
Glioma
Glioma Initiating Cells
Temozolomide
Tumor xenografts
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/7894/1/TargetingGliomaInitiatingCells_2018.pdf
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TargetingGliomaInitiatingCells_2018.pdf.txt