Navigation Links
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 with much less potency. That got Dr. Ganapathy thinking about a place where butyrate levels were already high the colon which led to his discovery that the receptor was also on colon cells.

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 disease hallmark.

"If you block HDAC, you can kill the cancer cell," Dr. Ganapathy says.

Several synthetic HDAC inhibitors are under study for a variety of cancers at institutions such as the MCG Cancer Center. Unfortunately, just like the newly found GPR109A receptor, cancer also silences the SLC5A8 butyrate transporter. In his current study, the researcher 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," Dr. 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.

Mega doses of butyrate reportedly taste bad. But Dr. 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.

He 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.


'/>"/>

Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

Related medicine news :

1. Diet high in meat, fat and refined grains linked to risk for colon cancer recurrence, death
2. Coloring Compound in Fruits, Veggies May Cut Colon Cancer Risk
3. Gastroenterology sets standards for CT colonography
4. Experts Compare Colon Cancer Treatment Outcomes
5. Doctors Office Outreach Boosts Colon Cancer Screening
6. Jefferson researchers find personalized interventions key to improving colon cancer screening rates
7. Molecular profiling can accurately predict survival in colon cancer patients
8. Study Links Coronary Disease, Colon Cancer
9. Fecal Blood Tests Effective at Spotting Colon Cancer
10. Produce for Better Health Foundation Releases Statement on Study Saying Fruit & Vegetable Consumption Not Strongly Associated With Colon Cancer Risk
11. Study makes progress in zoning in on biomarkers for better colon cancer treatment
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Colon cancer shuts down receptor that could shut it down
(Date:2/7/2016)... ... February 07, 2016 , ... Dr. ... Kybella® to his medical and surgical expertise. Technically known as deoxycholic acid or ... used as a non-surgical alternative for reduction of fat below the chin (aka ...
(Date:2/6/2016)... , ... February 06, 2016 , ... Shark Finds ... announce the launch of a new DRTV campaign with Belly Bands. , Having a ... everything from sprays to puppy pads and find nothing works, get Belly Bands, ...
(Date:2/5/2016)... (PRWEB) , ... February 05, 2016 , ... ... the availability of the company's lighter, sleeker next generation LYNX VR Indoor Trainer ... , Improvements in design and manufacturing not only reduce the weight of ...
(Date:2/5/2016)... , ... February 05, 2016 , ... ... domestic franchisees of Popeyes Louisiana Kitchen restaurants, launched the 14th annual “Appetite for ... kids and adults with muscular dystrophy, ALS and related diseases that severely limit ...
(Date:2/5/2016)... (PRWEB) , ... February 05, 2016 , ... After years ... General Hospital Burn Unit, plastic and cosmetic surgeon Dr. Wayne Carman transitioned to chief ... Hospital. He successfully completed his first three-year term as chief and began a second ...
Breaking Medicine News(10 mins):
(Date:2/5/2016)... , Feb. 5, 2016  As people age, it ... multitude of recommended screenings and tests that are linked ... priority. However, for the majority of aging individuals, hearing ... planning. For the 37.5 million American adults who report ... present to make hearing health a 2016 healthy aging ...
(Date:2/5/2016)... , Feb. 5, 2016  Aralez Pharmaceuticals Inc. ... of POZEN Inc. ("POZEN") and Tribute Pharmaceuticals Canada Inc. ("Tribute") ... and shareholders of Tribute. The combined company will operate ... company with operations in Canada , ... United States . Under the terms of the ...
(Date:2/5/2016)... , Feb. 5, 2016 Aethlon Medical, Inc. (Nasdaq: ... Chairman and CEO, will be presenting at Source Capital Group,s ... York, NY at 2:15 p.m. ET on Wednesday, ... Immunotherapy Panel discussion taking place at 3:15 p.m. ET. ... approximately one hour after the conclusion of the live event. ...
Breaking Medicine Technology: