Researchers from the University of South Carolina have shown that treatment with delta-9-tetrahydrocannabinol (THC), a cannabinoid found in the cannabis plant, prevented the development of colon cancers in mice. It was shown that THC suppressed inflammation in the colon, preventing the onset of cancers caused by a carcinogen.
Reporting in the paper, ‘Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production’, published in iScience, Drs Prakash Nagarkatt and Mitzi Nagarkatti at the University of South Carolina (UofSC) School of Medicine Columbia, show that delta-9-tetrahydrocannabinol (THC) attenuates colitis-associated colon cancer and colitis induced by anti-CD40. Working through cannabinoid receptor 2 (CB2), THC increases CD103 expression on dendritic cells DCs and macrophages and upregulates TGF-β1 to increase T regulatory cells (Tregs).
"The fact that we were able to show that treatment with THC prevents inflammation in the colon and at the same time inhibits the development of colon cancer supports the notion that inflammation and colon cancer are closely linked. Thus, in patients who are at a higher risk of developing colon cancer, THC or other anti-inflammatory agents may be beneficial," explained Prakash Nagarkatti.
The cannabinoids act through two receptors known as CB1 and CB2. The CB1 receptor is expressed in the brain where THC activation causes psychoactive effects. The second receptor, CB2, is expressed mainly on the immune cells, meaning that activation of CB2 receptors does not trigger psychoactivity.
THC-induced Tregs are necessary to remedy systemic IFNγ and TNFα caused by anti-CD40, but CB2-mediated suppression of APCs by THC quenches pathogenic release of IL-22 and IL-17A in the colon. By examining tissues from multiple sites, the researchers confirmed that THC affects DCs, especially in mucosal barrier sites in the colon and lungs, to reduce DC CD86. Using models of colitis and systemic inflammation they found that THC, through CB2, is a potent suppressor of aberrant immune responses by provoking coordination between APCs and Tregs.
"Our results showed that THC was acting through CB2 receptors, which is exciting and suggests that compounds that activate CB2 and cause no psychoactive effects may be beneficial to prevent IBD and colon cancer," said Mitzi Nagarkatti.
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