Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide
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 Gliom...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/7894 |
| Acceso en línea: | http://hdl.handle.net/20.500.12105/7894 |
| Access Level: | acceso abierto |
| Palabra clave: | Animals Antineoplastic Combined Chemotherapy Protocols Brain Neoplasms Cannabidiol Cell Line, Tumor Dronabinol Female Glioblastoma Humans Male Mice, Nude Neoplastic Stem Cells Temozolomide Tumor Cells, Cultured Xenograft Model Antitumor Assays |
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Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomideLópez-Valero, IsraelSaiz-Ladera, CristinaTorres, SofíaHernández-Tiedra, SoniaGarcía-Taboada, ElenaRodríguez-Fornés, FátimaBarba, MarinaDávila, DavidSalvador-Tormo, NélidaGuzmán, ManuelSepúlveda, Juan MSánchez-Gómez, PilarLorente, MarVelasco, GuillermoAnimalsAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsCannabidiolCell Line, TumorDronabinolFemaleGlioblastomaHumansMaleMice, NudeNeoplastic Stem CellsTemozolomideTumor Cells, CulturedXenograft Model Antitumor AssaysGlioblastoma 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.ElsevierInstituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)Fundación Mutua MadrileñaMinisterio de Economía y Competitividad (España)GW Pharma Ltd. (UK)Comunidad de Madrid (España)Fundación La Marató TV3Voices Against Brain Cancer (US)The Medical Cannabis Bike Tour Foundation (The Netherlands)20192019-07-1120182018-01-0120182018-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/7894reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES PI15 00339ES PS09 01401ES PI12 02248ES S2011 BMD-2308ES AP101042012 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/78942026-06-12T12:43:37Z |
| dc.title.none.fl_str_mv |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| title |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| spellingShingle |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide López-Valero, Israel Animals Antineoplastic Combined Chemotherapy Protocols Brain Neoplasms Cannabidiol Cell Line, Tumor Dronabinol Female Glioblastoma Humans Male Mice, Nude Neoplastic Stem Cells Temozolomide Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| title_short |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| title_full |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| title_fullStr |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| title_full_unstemmed |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| title_sort |
Targeting Glioma Initiating Cells with A combined therapy of cannabinoids and temozolomide |
| dc.creator.none.fl_str_mv |
López-Valero, Israel Saiz-Ladera, Cristina Torres, Sofía Hernández-Tiedra, Sonia García-Taboada, Elena Rodríguez-Fornés, Fátima Barba, Marina Dávila, David Salvador-Tormo, Nélida Guzmán, Manuel Sepúlveda, Juan M Sánchez-Gómez, Pilar Lorente, Mar Velasco, Guillermo |
| author |
López-Valero, Israel |
| author_facet |
López-Valero, Israel Saiz-Ladera, Cristina Torres, Sofía Hernández-Tiedra, Sonia García-Taboada, Elena Rodríguez-Fornés, Fátima Barba, Marina Dávila, David Salvador-Tormo, Nélida Guzmán, Manuel Sepúlveda, Juan M Sánchez-Gómez, Pilar Lorente, Mar Velasco, Guillermo |
| author_role |
author |
| author2 |
Saiz-Ladera, Cristina Torres, Sofía Hernández-Tiedra, Sonia García-Taboada, Elena Rodríguez-Fornés, Fátima Barba, Marina Dávila, David Salvador-Tormo, Nélida Guzmán, Manuel Sepúlveda, Juan M Sánchez-Gómez, Pilar Lorente, Mar Velasco, Guillermo |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) Fundación Mutua Madrileña Ministerio de Economía y Competitividad (España) GW Pharma Ltd. (UK) Comunidad de Madrid (España) Fundación La Marató TV3 Voices Against Brain Cancer (US) The Medical Cannabis Bike Tour Foundation (The Netherlands) |
| dc.subject.none.fl_str_mv |
Animals Antineoplastic Combined Chemotherapy Protocols Brain Neoplasms Cannabidiol Cell Line, Tumor Dronabinol Female Glioblastoma Humans Male Mice, Nude Neoplastic Stem Cells Temozolomide Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| topic |
Animals Antineoplastic Combined Chemotherapy Protocols Brain Neoplasms Cannabidiol Cell Line, Tumor Dronabinol Female Glioblastoma Humans Male Mice, Nude Neoplastic Stem Cells Temozolomide Tumor Cells, Cultured Xenograft Model Antitumor Assays |
| description |
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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2018-01-01 2018 2018-01-01 2019 2019-07-11 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/20.500.12105/7894 |
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http://hdl.handle.net/20.500.12105/7894 |
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Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
ES PI15 00339 ES PS09 01401 ES PI12 02248 ES S2011 BMD-2308 ES AP101042012 Not available |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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reponame:Repisalud instname:Instituto de Salud Carlos III (ISCIII) |
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Instituto de Salud Carlos III (ISCIII) |
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Repisalud |
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Repisalud |
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