Title |
Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma
|
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Published in |
Molecular Cancer Therapeutics, July 2009
|
DOI | 10.1158/1535-7163.mct-08-1147 |
Pubmed ID | |
Authors |
Susanne Oesch, Dagmar Walter, Marco Wachtel, Kathya Pretre, Maria Salazar, Manuel Guzmán, Guillermo Velasco, Beat W. Schäfer |
Abstract |
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 Delta(9)-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. |
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Country | Count | As % |
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United States | 6 | 50% |
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Unknown | 5 | 42% |
Demographic breakdown
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Science communicators (journalists, bloggers, editors) | 1 | 8% |
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Mendeley readers
Geographical breakdown
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Switzerland | 1 | 2% |
Germany | 1 | 2% |
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United States | 1 | 2% |
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Researcher | 14 | 22% |
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Professor | 4 | 6% |
Student > Master | 4 | 6% |
Other | 11 | 17% |
Unknown | 8 | 13% |
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Physics and Astronomy | 2 | 3% |
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