RT Journal Article
T1 A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma
A1 Torres, Sofia
A1 Lorente Pérez, María Del Mar
A1 Rodríguez Fornés, Fátima
A1 Hernández Tiedra, Sonia
A1 Salazar Roa, María
A1 García Taboada, Elena
A1 Barcia Albacar, Juan Antonio
A1 Guzmán Pastor, Manuel
A1 Velasco Díez, Guillermo
AB Glioblastoma multiforme (GBM) is highly resistant to current anticancer treatments, which makes it crucial to find new therapeutic strategies aimed at improving the poor prognosis of patients suffering from this disease. Δ9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoid receptor agonists inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the stimulation of autophagy-mediated apoptosis in tumor cells. Here, we show that the combined administration of THC and temozolomide (TMZ; the benchmark agent for the management of GBM) exerts a strong antitumoral action in glioma xenografts, an effect that is also observed in tumors that are resistant to TMZ treatment. Combined administration of THC and TMZ enhanced autophagy, whereas pharmacologic or genetic inhibition of this process prevented TMZ + THC-induced cell death, supporting that activation of autophagy plays a crucial role on the mechanism of action of this drug combination. Administration of submaximal doses of THC and cannabidiol (CBD; another plant-derived cannabinoid that also induces glioma cell death through a mechanism of action different from that of THC) remarkably reduces the growth of glioma xenografts. Moreover, treatment with TMZ and submaximal doses of THC and CBD produced a strong antitumoral action in both TMZ-sensitive and TMZ-resistant tumors. Altogether, our findings support that the combined administration of TMZ and cannabinoids could be therapeutically exploited for the management of GBM.
PB American Association for Cancer Research
SN 1535-7163
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/97869
UL https://hdl.handle.net/20.500.14352/97869
LA eng
NO Sofía Torres, Mar Lorente, Fátima Rodríguez-Fornés, Sonia Hernández-Tiedra, María Salazar, Elena García-Taboada, Juan Barcia, Manuel Guzmán, Guillermo Velasco; A Combined Preclinical Therapy of Cannabinoids and Temozolomide against Glioma. Mol Cancer Ther 1 January 2011; 10 (1): 90–103. https://doi.org/10.1158/1535-7163.MCT-10-0688
NO AcknowledgmentsWe thank Horacio Zimman and Carmen Moreno, from Hospital Clínico San Carlos, as well as Leyre Urigüen, from Universidad del Pais Vasco, for their kind collaboration in the processing and delivery of glioma samples; Dolores Hernán, Ana Isabel Torres, and Esther Gil for their contribution to the development of experiments with microparticles, and other members of our laboratory for their continuous support.Grant SupportThis work was supported by grants from Spanish Ministry of Science and Innovation (MICINN; PS09/01401; HF2005/0021, FR2009-0052, and IT2009-0053 to G. Velasco; SAF2006/00918 to M. Guzman), Santander-Complutense (PR34/07-15856 to G. Velasco), Comunidad de Madrid (S-SAL/0261/2006 and 950344 to M.G.), GW Pharmaceuticals (G. Velasco and M. Guzman), and Schering-Plough (G. Velasco). S. Torres was a recipient of a research training contract from Comunidad de Madrid; M. Lorente was sequentially a recipient of a “Juan de la Cierva” contract, a postdoctoral contract from Spanish Ministry of Education and Science and a postdoctoral contract from Comunidad de Madrid. F. Rodríguez-Fornés was a recipient of a fellowship from Schering-Plough and GW Pharmaceuticals; M. Hernández-Tiedra was a recipient of a fellowship from MEC and of a research training contract from Comunidad de Madrid; S. Hernández-Tiedra has a technician contract from MICINN and Fondo Social Europeo.
NO Schering-Plough
NO GW Pharmaceuticals
NO Comunidad de Madrid
NO Ministerio de Ciencia e Innovación  (España)
NO European Commission
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 10 abr 2025