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oai:docta.ucm.es:20.500.14352/976502025-03-18T12:25:43Zcom_20.500.14352_14col_20.500.14352_15

Oesch, Susanne Walter, Dagmar Wachtel, Marco Pretre, Kathya Salazar Roa, María Guzmán Pastor, Manuel Velasco Díez, Guillermo Schäfer, Beat 2024-02-01T12:16:43Z 2024-02-01T12:16:43Z 2009 Susanne Oesch, Dagmar Walter, Marco Wachtel, Kathya Pretre, Maria Salazar, Manuel Guzmán, Guillermo Velasco, Beat W. Schäfer; Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma. Mol Cancer Ther 1 July 2009; 8 (7): 1838–1845. https://doi.org/10.1158/1535-7163.MCT-08-1147 1535-7163 10.1158/1535-7163.MCT-08-1147 https://hdl.handle.net/20.500.14352/97650 https://doi.org/10.1158/1535-7163.MCT-08-1147 Gene expression profiling has revealed that the gene coding for cannabinoid receptor 1 (CB1) is highly up-regulated in rhabdomyosarcoma biopsies bearing the typical chromosomal translocations PAX3/FKHR or PAX7/FKHR. Because cannabinoid receptor agonists are capable of reducing proliferation and inducing apoptosis in diverse cancer cells such as glioma, breast cancer, and melanoma, we evaluated whether CB1 is a potential drug target in rhabdomyosarcoma. Our study shows that treatment with the cannabinoid receptor agonists HU210 and Δ9-tetrahydrocannabinol lowers the viability of translocation-positive rhabdomyosarcoma cells through the induction of apoptosis. This effect relies on inhibition of AKT signaling and induction of the stress-associated transcription factor p8 because small interfering RNA–mediated down-regulation of p8 rescued cell viability upon cannabinoid treatment. Finally, treatment of xenografts with HU210 led to a significant suppression of tumor growth in vivo. These results support the notion that cannabinoid receptor agonists could represent a novel targeted approach for treatment of translocation-positive rhabdomyosarcoma eng restricted access Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma journal article