Fiber helps kill bad cells

It has long been known that eating a lot of fiber helps lower the risk of colon cancer. But exactly how that worked hasn't been known -- until now.

Research at Medical College of Georgia published online this month in Cancer Research is focusing on a chemical fermented from fiber in the colon that works with a protein on the colon cell surface to kill cancer cells.

In an unrelated paper published online today in the Journal of Clinical Investigation, a team at Duke University Medical Center is looking at how to enhance the same cell surface protein's effect on lowering bad cholesterol and increasing good cholesterol through niacin, or vitamin B3. That team might turn its attention to potential cancer protective effects after seeing MCG's work.

MCG's work seeks a better understanding of the relationship between people and the bacteria in their colons. It used to be thought that the bacteria were just taking advantage of the situation, said Vadivel Ganapathy, the chairman of the Department of Biochemistry and Molecular Biology at MCG.

"It is like teenage kids in the house," Dr. Ganapathy said, laughing. "We cohabitate; we provide them everything; but they don't do anything in return for us."

But it turns out there is more of an interactive, symbiotic relationship between the bacteria and the host, and one way is through the breakdown of fiber by the bacteria into useful chemicals. One of those, called butyrate, is a natural inhibitor of histone deacetylase, a cancer-causing process.

"The idea is that the bacteria, using the fiber you take in the diet, produces this histone deacetylase inhibitor," Dr. Ganapathy said. "The fiber and the bacteria together gives you protection against colon cancer.'

It works in two different ways: Dr. Ganapathy and his team found a transporter that carries the chemical into the cell to do its work; there is also a protein on the surface of the cells, g-protein-coupled receptor 109A, that starts a process that results in cancer-cell death when it is activated by butyrate.

Dr. Ganapathy found human colon cancer cells manage to turn off both processes. The MCG team is now breeding mice that lack both to test their theories.

Butyrate had been known as a histone deacetylase inhibitor but was not considered very effective because it is difficult to build up high enough concentrations in the blood for it to have an effect, said Dr. Kapil Bhalla, the director of the MCG Cancer Center and an associate editor of Cancer Research.

"But in the gut it can. It's very effective," he said.

The cell surface protein GPR109A is also known as the mechanism by which niacin helps lower cholesterol by preventing fat cells from releasing fatty acid, Dr. Ganapathy said. It is one of the cheapest and most effective ways to do that, and boost good cholesterol, but there is a catch in that it causes skin to flush, said Duke researcher Robert W. Walters.

"One of the problems that we see is that about 80 percent of the people who take that drug, they wind up having to stop it just because the flushing events are a real nuisance," he said. "It's not a trivial side effect."

The Duke team was able to locate and isolate another protein responsible for the flushing and hope to create a drug that doesn't cause it. Dr. Walters said he is also intrigued by the potential cancer-protective effects.

"(Niacin) was the first one to ever be shown to have a beneficial effect on mortality," he said. "Some of that probably relates to the lipid effect. It's possible that some of it relates to the apoptotic (inducing cancer cell death) effect, the sort of protective effect from other things, too. It's a great question. It is certainly an area open for investigation."

If nothing else, Dr. Ganapathy said, it should reinforce the need to get fiber in your diet -- if not for you, then for your bacteria.

"The bottom line is, we ought to keep our normal bacteria happy and healthy in order to get the beneficial effects from them," he said.

Reach Tom Corwin at (706) 823-3213 or tom.corwin@augustachronicle.com.