Though a high-fiber diet has long been considered good for you and beneficial in staving off colon cancer, researchers at the Medical College of Georgia have discovered why. They say they have found that roughage activates a receptor with cancer-killing potential. They report that butyrate, a metabolite produced by fiber-eating bacteria in the colon, activates a receptor that sends signals that trigger cell death or apoptosis in cancer cells. These signals also shut 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 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 known as GPR109A by chemically modifying its gene through a process called DNA methylation. DNA methylation inhibitors already are under study for a variety of cancers.

 

In the study published in the April issue of Cancer Research, the investigators say 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. One of those activators, niacin, a B-complex vitamin, led to his discovery of the relationship between butyrate and GPR109A.

 

Butyrate plays other protective roles in colon cancer. In 2004, MCG researchers identified a gene, SLC5A8, that transports butyrate inside cells where it inhibits the enzyme HDAC, which gets upregulated in cancer to produce the uncontrolled cell growth that is a hallmark of the disease. Several synthetic HDAC inhibitors are under study for a variety of cancers at institutions such as the MCG Cancer Center. Like the newly found GPR109A receptor, cancer also silences the SLC5A8 butyrate transporter. In his current study, Ganapathy found the receptor was silenced in 15 of 18 colon cancer patients.

 

“Colon cancer does not want butyrate produced by bacteria to come inside so it silences the transporter. It also does no want butyrate to act on the cell from the outside so it silences the receptor,” Ganapathy says. “It does not want to have anything to do with butyrate.”

 

Because the compounds that reactivate the receptor also reactivate the transporter, finding a way to mitigate cancer's attempts to silence the genes would create a two-prong attack against the cancer. Megadoses of butyrate reportedly taste bad. But Ganapathy believes taking large amounts of niacin, something many patients already do for high cholesterol, is a good substitute. In fact, he wants to move ahead with clinical trials that compare the course of colon cancer patients who eat a high-fiber diet or receive butyrate or niacin therapy along with taking DNA methylation inhibitors that keep GPR109A open for business.

 

Ganapathy also wants to determine if his theory that inflammation also suppresses the receptor holds true. "We think receptor activation by butyrate suppresses inflammation, thereby suppressing progression of inflamed cells into cancer cells." If he's correct, targeting the receptor also may provide a new treatment for inflammatory bowel disease.