1 August 2008
Raymond DuBois and colleagues at the University of Texas in Houston discovered that a key receptor for cannabinoids, which are found in marijuana, is turned off in most types of human colon cancer.
Without this receptor, a protein called survivin, which stops cells from dying, increases unchecked and causes tumour growth.
To better understand the role that the receptor, called CB1, plays in cancer progression, the researchers manipulated its expression in mice that had been genetically engineered to spontaneously develop colon tumours.
“When we knocked out the receptor, the number of tumors went up dramatically,” says DuBois. Alternatively, when mice with normal CB1 receptors were treated with a cannabinoid compound, their tumours shrank.
The findings suggest a two-step treatment plan for colon cancer, as well as for other cancers that might be linked to this receptor.
First, turn the CB1 receptor back on, and then activate it with drugs currently in development that mimic marijuana. But how to turn it on?
The researchers found that in human colon cancer cells, the gene that makes the receptor is blocked by a process called methylation, in which a small chemical group is added to the DNA.
Treating the cells with decitibine – a demethylating drug already approved for use in humans – removed the chemical group and the gene began making the receptor. Drugs that mimic marijuana might then activate the receptor, although DuBois did not test this.
Journal reference: Cancer Research (vol 68, p 6468)