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Cell Receptor Is Absent in Colorectal Cancer

CancerWise - January 2009

A cell surface receptor of cannabinoids, which are used to relieve pain and nausea caused by cancer treatment, also may help prevent or treat colorectal cancer.

Researchers have found that CB1, which serves as a docking station for cannabinoid molecules, is not present in colorectal cancer tumors. Cannabinoids are well established for relieving pain and nausea, elevating mood and stimulating appetite.

Scientists at M. D. Anderson and the Vanderbilt-Ingram Cancer Center published the research in the Aug. 1 edition of the journal Cancer Research.

Significance of results

"Potential application of cannabinoids as anti-tumor drugs is an exciting prospect," says senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president at M. D. Anderson.

"Turning CB1 back on and then treating with a cannabinoid agonist (a substance that causes a physiological response when combined with a receptor) could provide a new approach to colorectal cancer treatment or prevention."

Cannabinoids can come from a variety of sources.

These include:

  • The body (called endocannabinoids)
  • Pharmaceuticals
  • Plants, including the active ingredient in marijuana (THC)

Background

Endocannabinoid signaling is important to the normal functioning of the digestive system and has been shown to protect the colon against inflammation. Since chronic inflammation is a known risk factor for colorectal cancer, the researchers decided to look into the role of cannabinoid receptors.

Cannabinoids previously have been shown to kill cancer cells in lab experiments.

Research methods

Researchers injected human colorectal tumors into mice, then measured levels of CB1.

Primary results

CB1 was largely absent in:

  • 18 of 19 tumors
  • 9 of 10 colorectal cancer cell lines

The gene that controls the CB1 protein was not damaged, but it was shut down chemically by the attachment of methyl groups (a carbon atom surrounded by three hydrogen atoms).

Treating cell lines with decitabine, a drug approved for some types of leukemia, removed the methyl groups, restoring the gene in seven of eight cell lines and the CB1 protein in three lines.

Additional results

Deletion of the CB1 gene in a type of mouse that spontaneously develops precancerous colorectal polyps resulted in:

  • 2.5-to-3.8-fold increase in the number of polyps
  • Tenfold increase in growths likely to become cancer

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

The team analyzed the other main cannabinoid receptor, CB2, and found no role for it in colorectal cancer.

What’s next?

Further investigation, the researchers note, is needed to define the role of CB1 in colorectal and other types of cancer.

— Adapted by Dawn Dorsey from an M. D. Anderson news release

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© 2014 The University of Texas MD Anderson Cancer Center