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

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma Oesch, Susanne Walter, Dagmar Wachtel, Marco Pretre, Kathya Salazar Roa, María Guzmán Pastor, Manuel Velasco Díez, Guillermo Schäfer, Beat 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 2024-02-01T12:16:43Z 2024-02-01T12:16:43Z 2024-02-01T12:16:43Z 2009 journal article https://hdl.handle.net/20.500.14352/97650 1535-7163 10.1158/1535-7163.MCT-08-1147 eng 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 restricted access American Association Cancer Research