A biologic mechanism in yeast cells may explain the relationship between sugar and malignant tumors, according to a recent study published in the journal Nature Communications.
Scientists understand that cancer cells support their rapid reproduction by rewiring their metabolisms to take glucose, ferment it and produce lactate.
Conversely, healthy cells continue with normal respiration, a process in which they take glucose and break it down into carbon dioxide and water.
This "switch of cancer cells from respiration to fermentation is something that was discovered by Otto Warburg, a German biochemist, about 70 or 80 years ago," said microbiologist Johan M. Thevelein, senior author of the study and a professor at KU Leuven in Belgium. It is known as "the Warburg effect."
Fermentation of sugar to lactic acid produces about 15 times less energy than respiration of sugar, Thevelein noted. Yet cancer cells "grow much more rapidly than normal cells, and yeast actually grows the fastest when they ferment," he noted.
"This is weird," he said, and it raises an important question: Is the Warburg effect a symptom of cancer -- or a cause of it?
Searching for the answer, Thevelein and his colleagues experimented with yeast cells since, just like cancer cells, they are known to favor fermentation over respiration.
The researchers found an intermediate compound that is a "potent activator" of the RAS protein. RAS is a proto-oncogene: a gene that codes for proteins that help to regulate cell growth and differentiation. Proto-oncogenes can become oncogenes or cancer-causing genes when mutations occur. Mutant forms of RAS proteins are present in many tumors, Thevelein said.
The new study, then, reveals "a vicious cycle," he said.
As sugar is broken down in cells, the intermediate compound activates the RAS proteins, and this in turn stimulates cell proliferation, he said.
This cycle seen in yeast cells might help explain the aggressiveness of cancer.
"Very interesting," said Dr. Jennifer Ligibel, chairwoman of the American Society of Clinical Oncology's energy balance committee. Still, she urges caution in interpreting these findings.
"It's important to not make too many jumps into a patient message based on a study of yeast," she said.
Sugar can cause obesity which leads to cancer
Asked whether he believes that eating more sugar leads to more cancer, Thevelein immediately answered, "No! definitely not." He and his co-authors do not state that in the paper; instead, they explain how normal, healthy cells can handle sugar in a controlled way.
"On the other hand, we all know that when you eat a lot of sugar, you have a tendency -- that has been clearly shown -- to become more obese," Thevelein said. "And obesity is linked to a higher risk of cancer."
Though it's "too early to say," Thevelein said that when you eat too much sugar over a long time, "maybe this can also lead in some way to dysregulation of the RAS protein in the normal cells," and possibly it is this "dysregulation" that triggers RAS genes into becoming mutants.
"It's better not to eat too much sugar so that you don't become obese," he said. "And if at the same time, you also decrease your risk of cancer, the better -- but this is something we cannot make a statement about at this moment."
If anything, he would suggest that cancer patients eat less simple sugars and more complex sugars, such as those found in starch and whole grains. Complex sugars are released more slowly and are taken up by the body more slowly, and this might be helpful to cancer patients.
"That would be our message," Thevelein said: "Try to look for alternative ways of providing sugar and energy to cancer patients rather than rapidly metabolized simple sugars."
Highlights
• Healthy cells and cancer cells metabolize glucose differently
• A cycle seen in yeast cells might help explain the aggressiveness of cancer
• Eating sugar doesn't necessarily raise cancer risk, but obesity can
