Cannabis Research A-Z

Biochem Soc Trans.  2005; 33(Pt 4):712-4 (ISSN: 0300-5127)

Patsos HA; Hicks DJ; Greenhough A; Williams AC; Paraskeva C

Cancer Research UK Colorectal Tumour Biology Group, Department of Cellular and Molecular Medicine,

School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. helena.patsos@bristol.ac.uk

Despite extensive research into the biology of CRC (colorectal cancer), and recent advances in surgical techniques and chemotherapy, CRC continues to be a major cause of death throughout the world.

Therefore it is important to develop novel chemopreventive/chemotherapeutic agents for CRC. Cannabinoids are a class of compounds that are currently used in the treatment of chemotherapy-induced nausea and vomiting, and in the stimulation of appetite.

 However, there is accumulating evidence that they could also be useful for the inhibition of tumour cell growth by modulating key survival signalling pathways. The chemotherapeutic potential for plant-derived and endogenous cannabinoids in CRC therapy is reviewed.

Major Subject Heading(s)	Minor Subject Heading(s)	CAS Registry / EC Numbers
	Antiemetics [therapeutic use] Antineoplastic Agents [adverse effects] [therapeutic use] Cannabinoids [therapeutic use] Colorectal Neoplasms [drug therapy] Humans Nausea [prevention & control] Vomiting [prevention & control]   Top      Home	0  (Antiemetics) 0  (Antineoplastic Agents) 0  (Cannabinoids)

The chemicals in marijuana could put the brakes on colon cancer, according to new research. That doesn't mean smoking a joint will help, though, as the chemicals only form part of the process.

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.

Dual attack

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.

 

06 August 2008 Magazine issue 2668.

SMOKING hash or marijuana may not be the healthiest way to do it, but taking substances similar to those found in cannabis might one day help to treat colon cancer.

Raymond DuBois and colleagues at the University of Texas, Houston, discovered that a key receptor for cannabinoids - compounds similar to the active ingredient of cannabis - is turned off in most types of human colon cancer cells.

Similarly, mice genetically engineered to develop colon tumours developed more of them if the receptor, called CB1, was knocked out (Cancer Research, DOI: 10.1158/0008-5472.CAN-08-0896). What's more, tumours shrank when the genetically engineered mice were injected with a cannabinoid.

One suggestion is that lack of CB1 encourages tumour growth because the receptor normally interacts with cannabinoids made by the body to prompt cells to die. This opens up a possible two-step treatment for colon cancer. First, switch CB1 back on using...

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Findings may serve as new path for better treatment of disease, study suggests

FRIDAY, Aug. 1 (HealthDay News) -- A cannabinoid receptor lying on the surface of cells may help suppress colorectal cancer, say U.S. researchers. When the receptor is turned off, tumor growth is switched on.

Cannabinoids are compounds related to the tetrahydrocannabinol (THC) found in the cannabis plant.

It's already known that the receptor, CB1, plays a role in relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. This study suggests that CB1 may offer 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," senior author Dr. Raymond Dubois, provost and executive vice president of the University of Texas M.D. Anderson Cancer Center, said in a university news release.

In their study of human colorectal tumor specimens, the researchers also found that the drug decitabine can restore CB1 expression.

In addition, mice that are prone to developing intestinal tumors and also have functioning CB1 receptors developed fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand, the researchers found. Ligands are molecules that function by binding to specific receptors.

"Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists (synthetic molecules that mimic the action of natural molecules) are being evaluated now to treat the side effects of chemotherapy and radiation therapy," DuBois said. "Turning CB1 back on and than treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention."

The study was published in the Aug. 1 issue of the journal Cancer Research.

More information

The American Cancer Society has more about colorectal cancer.

-- Robert Preidt Copyright © 2008 ScoutNews, LLC. All rights reserved.
Last updated 8/1/2008

 

 

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Pharmacol Res. 2009 Aug;60(2):117-25. Epub 2009 Mar 18.

Izzo AA, Camilleri M.

Department of Experimental Pharmacology, University of Naples Federico II and Endocannabinoid Research Group, Naples, Italy. aaizzo@unina.it

1. H A Patsos
2. D J Hicks
3. R R H Dobson
4. A Greenhough
5. N Woodman
6. J D Lane
7. A C Williams
8. C Paraskeva
9. Correspondence to:
   Professor C Paraskeva
   Cancer Research UK, Colorectal Tumour Biology Group, Department of Pathology and Microbiology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, UK; C.Paraskeva@bristol.ac.uk
10. Accepted 5 July 2005
11. Revised 24 June 2005
12. Published Online First 11 August 2005