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Colon cancer shuts down receptor that could shut it down
Date:4/13/2009

AUGUSTA, Ga. Though a high-fiber diet has long been considered good for you and beneficial in staving off colon cancer, Medical College of Georgia researchers have discovered a reason why: roughage activates a receptor with cancer-killing potential.

Researchers report in the April issue of Cancer Research that the GPR109A receptor is activated by butyrate, a metabolite produced by fiber-eating bacteria in the colon. The receptor puts a double-whammy on cancer by sending signals that trigger cell death, or apoptosis, and shutting down a protein that causes inflammation, a precursor to cancer.

"We know the receptor is silenced in cancer but it's not like the gene goes away," says Dr. Vadivel Ganapathy, corresponding author and chair of the Department of Biochemistry and Molecular Biology in the MCG School of Medicine.

Cancer shuts down the receptor by chemically modifying its gene through a process called DNA methylation. It's a typical MO for cancer to turn genes off to suit its purpose which is why DNA methylation inhibitors already are under study for a variety of cancers.

But cancer patients likely also need something to ensure the receptor gets activated by butyrate, such as eating more roughage or, more likely, getting mega doses of butyrate or a compound with similar properties, Dr. Ganapathy says.

One of those activators, niacin, a B-complex vitamin, led to his discovery of the relationship between butyrate and GPR109A. Research teams at GlaxoSmithKline and the University of Heidelberg, Germany in 2003 showed cloned GPR109A mediated the protective cardiovascular effect of niacin, but was activated only if niacin levels in the blood were 1,000 times normal levels. That got the German research team to search for alternative activators of the receptor, resulting in identification of beta-hydroxybutyrate as a natural receptor activator. The same study showed butyrate also could activate the receptor but
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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