High-Fructose Corn Syrup Enhances Intestinal Tumorigenesis in Mice

Consuming the equivalent of one can of soda per day caused mice predisposed to colon cancer to develop larger tumors, according to a study by Weill Cornell Medicine and NewYork-Presbyterian investigators.  The study, published today in Science, shows how high-fructose corn syrup fuels the growth of colon tumors in these mice and demonstrated a potential strategy to block this excess tumor growth.

"The study shows that colorectal polyps feed on high fructose corn syrup and explains the molecular mechanism by which this drives the growth of the tumor," said co-senior author Dr. Lewis Cantley. "While our work was conducted in mice, our findings build on mounting evidence that sugar fuels cancer growth."

In their study, the researchers squirted a small dose of high-fructose corn syrup each day for eight to nine weeks into the mouths of mice genetically engineered to develop colon tumors. This dose is the mouse equivalent of drinking one soda per day, which about half of Americans do, Dr. Goncalves said. These mice did not become obese or develop metabolic syndrome. The investigators then compared the tumors that developed in the sugar-fed mice with tumors in mice with the same predisposition to colon tumors but no added sugar in their diet. They found that the sugar-fed mice developed more large tumors compared with the control mice.

"We were not able to show that giving high-fructose syrup causes new tumors because these mice develop tumors even on normal diets free of added sugar," Dr. Goncalves cautioned. "But when you give them this additional sugar, the tumors grow much bigger."

To understand why, they looked at what happens when mice are fed high-fructose corn syrup. Consuming the sweetener delivers an excess of both glucose and fructose to the colon of the mice. By using isotope-labeled sugars, Dr. Cantley and his team showed colon tumors readily take in both sugars. Ketohexokinase (KHK) changes the fructose into fructose-1-phosphate, which makes it easier for the tumor to use glucose for energy. This also promotes the production of fats necessary for tumors to grow. Both the fats and the fructose-1-phosphate promote more tumor growth.

Deleting the gene for KHK or a gene called fatty acid synthase, which is responsible for producing fats that are essential for making the membranes that surround new cancer cells, in mice genetically engineered to develop colon tumors prevents the tumor growth-promoting effects of high-fructose corn syrup.

This may suggest that drugs targeting KHK or fat production in tumor cells may help reverse the tumor-growing effects of these sugars in people. One potential way to determine whether this would be effective is to randomize patients to receive a KHK-blocking drug, which is currently in Phase II clinical trials for fatty liver disease. Another approach would be to test whether a very low-sugar diet, like the ketogenic diet, slows tumor growth, Dr. Goncalves said.