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Mol Cancer Ther. 2009 Jul;8(7):1838-45. doi: 10.1158/1535-7163.MCT-08-1147. Epub 2009 Jun 9.

Cannabinoid receptor 1 is a potential drug target for treatment of translocation-positive rhabdomyosarcoma.

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1
Department of Oncology, University Children's Hospital, Zurich, Switzerland.

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.

PMID:
19509271
DOI:
10.1158/1535-7163.MCT-08-1147
[Indexed for MEDLINE]
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