Cannabinoid receptor suppress tumour growth in colorectal cancer

Washington, Aug 1 : A new study from the University of Texas M. D. Anderson Cancer Centre has shown that the cannabinoid cell surface receptor CB1 plays a key role in suppressing tumour growth in colorectal cancer patients.

The researchers hope that the new find may serve as a new path for cancer prevention or treatment.

"We've found that CB1 expression is lost in most colorectal cancers, and when that happens a cancer-promoting protein is free to inhibit cell death," said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of The University of Texas M. D. Anderson Cancer Center.

DuBois and collaborators from Vanderbilt-Ingram Cancer Center found that that CB1 expression can be restored with an existing drug, decitabine.

In the study conducted using a mouse model showed that mice prone to developing intestinal tumors that also have functioning CB1 receptors develop fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand.

Ligands are molecules that function by binding to specific receptors. Agonists are synthetic molecules that mimic the action of a natural molecule.

"Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists are being evaluated now to treat the side-effects of chemotherapy and radiation therapy," DuBois said.

"Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention," he added.

The group found that deletion of the CB1 gene in a strain of mice that spontaneously develops precancerous polyps resulted in a 2.5-to-3.8-fold increase in the number of polyps and a 10-fold increase in the number of large growths, those most likely to develop into cancer.

Treating mice that had the CB1 receptor with an endocannabinoid agonist resulted in a decline in polyps ranging from 16.7 percent to 50 percent. The reduction was greater for larger polyps.

A series of experiments showed that CB1 increases cancer cell death by stifling a protein called survivin.

DuBois said that survivin is overexpressed in nearly every human tumour but is barely detectable in normal tissue. Overexpression of survivin is associated with poor outcome and reduced apoptosis in colorectal cancer patients. The researchers pinpointed a cell signaling pathway by which activated CB1 cuts down survivin.

The study is published in the Aug. 1 edition of the journal Cancer Research.

ANI