Colorectal cancer is the fourth leading cause of cancer and cancer-related deaths in the world. Yet most colorectal cancer occurs in industrialized nations, says Dr. Giovanni Pitari, lead author of the study and a professor of clinical pharmacology at Thomas Jefferson University in Philadelphia.
The incidence of colorectal cancer is lowest in underdeveloped countries, where E. coli infections are the most common. Pitari and his colleagues reasoned that something about E. coli might ward off colorectal cancer.
E. coli produces heat-stable enterotoxins, toxic by-products that are resistant to high temperatures. To test their theory, researchers placed enterotoxins into colon cancer cells grown in the laboratory.
They found enterotoxins inhibited the growth of the colon cancer cells.
"We found the toxin doesn't cause cell death, but it does reduce the proliferation of colon cancer cells," Pitari says.
The study appears in the Feb. 10 issue of the Proceedings of the National Academy of Sciences.
Researchers also delved further into the mechanism of how enterotoxins prevent the growth of colon cancer cells. What they learned may one day lead to the development of new treatments for colon cancer, Pitari says.
When E. coli enters the body, the enterotoxins it produces target a specific receptor (GC-C receptor) found in the lining of the intestines. The toxin binds to the receptor, causing the secretion of electrolytes and water, and, hence, diarrhea.
When enterotoxins encounter colon cancer cells, the toxins bind to the same receptor, but what's triggered inside the cell is different. With the tumor cells, the enterotoxins set off a cascade of events inside that cell that inhibit its growth.
Most of the deaths from colorectal cancer occur when it has metastasized, or spread, to other organs. Theoretically, doctors could inject enterotoxins intravenously, which would then target the colon cancer cells throughout the body.
The enterotoxins would be harmless to other organs, because GC-C receptor that the toxins target are found only in the intestines and thus in the colon cancer cells.
Pitari emphasized that his work was in the lab. The next stage is animal and, later, human tests.
"Sometimes, what you see in vitro seems really promising, but you don't see the same effects in animals or human," he says.
Stephen Carrithers, an assistant professor of medicine at the University of Kentucky and a colon cancer researcher, says it's important to remember that there is still no direct evidence linking E. coli and lower colon cancer risk in the real world. Another pathogen, rotavirus, is to blame for the most deaths due to diarrhea in underdeveloped nations, he adds.
"There just hasn't been an epidemiological study that shows people chronically infected with E. coli really do have lower rates of colon cancer," says Carrithers, who wrote a commentary about the study that appeared in the same issue of the journal.
However, Pitari's findings are promising, Carrithers says. "In the laboratory, he's shown something secreted from E. coli does prevent the progression of colorectal cancer."
Previous studies, he notes, have actually shown that enterotoxins cause cell death.
Carrithers says it's possible that some day, people could take enterotoxin supplements to prevent colorectal cancer. "You might be able to give people low amounts all the time that would keep the colorectal cancer from ever forming."