Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth
- 1 August 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 68 (15), 6468-6476
- https://doi.org/10.1158/0008-5472.can-08-0896
Abstract
Although endocannabinoid signaling is important for certain aspects of gastrointestinal homeostasis, the role of the cannabinoid receptors (CB) in colorectal cancer has not been defined. Here we show that CB1 expression was silenced in human colorectal cancer due to methylation of the CB1 promoter. Our genetic and pharmacologic studies reveal that loss or inhibition of CB1 accelerated intestinal adenoma growth in ApcMin/+ mice whereas activation of CB1 attenuated intestinal tumor growth by inducing cell death via down-regulation of the antiapoptotic factor survivin. This down-regulation of survivin by CB1 is mediated by a cyclic AMP–dependent protein kinase A signaling pathway. These results indicate that the endogenous cannabinoid system may represent a potential therapeutic target for prevention or treatment of colorectal cancer. [Cancer Res 2008;68(15):6468–76]Keywords
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This publication has 42 references indexed in Scilit:
- Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colonJournal of Molecular Medicine, 2007
- Endocannabinoid overactivity and intestinal inflammationGut, 2006
- New Pathways from PKA to the Cdc2/cyclin B Complex in Oocytes: Wee1B as a Potential PKA SubstrateCell Cycle, 2005
- Cannabinoids and cancer: potential for colorectal cancer therapyBiochemical Society Transactions, 2005
- Cannabinoids and cancer: causation, remediation, and palliationThe Lancet Oncology, 2005
- Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in GliomasCancer Research, 2004
- Endogenous cannabinoid system as a modulator of food intakeInternational Journal of Obesity, 2003
- Validating survivin as a cancer therapeutic targetNature Reviews Cancer, 2003
- IAP proteins: blocking the road to death's doorNature Reviews Molecular Cell Biology, 2002
- Immunohistochemical Detection of the Anti-Apoptosis Protein, Survivin, Predicts Survival After Curative Resection of Stage II Colorectal CarcinomasAnnals of Surgical Oncology, 2001