Post by Admin on Feb 3, 2019 15:21:04 GMT
Loss of Cannabinoid Receptor 1 Accelerates Intestinal Tumor Growth
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Abstract
Although endocannabinoid signaling is important for certain aspects of gastrointestinal homoeostasis, 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 downregulation of the anti-apoptotic factor survivin. This downregulation of survivin by CB1 is mediated by a cAMP-dependent PKA signaling pathway. These results indicate that the endogenous cannabinoid system may represent a potential therapeutic target for prevention or treatment of colorectal cancer.
Source: www.ncbi.nlm.nih.gov/pmc/articles/PMC2561258/
Go to:
Abstract
Although endocannabinoid signaling is important for certain aspects of gastrointestinal homoeostasis, 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 downregulation of the anti-apoptotic factor survivin. This downregulation of survivin by CB1 is mediated by a cAMP-dependent PKA signaling pathway. These results indicate that the endogenous cannabinoid system may represent a potential therapeutic target for prevention or treatment of colorectal cancer.
Source: www.ncbi.nlm.nih.gov/pmc/articles/PMC2561258/