Bacterial toxin may fend off colon cancer. (Montezuma's Welcome Revenge?).

Some microbes that cause diarrhea may have important beneficial consequences. Researchers have found that the illness-inducing toxin from some strains of the common gut bacterium, Escherichia coli, stifles the growth of cancerous intestinal cells. This discovery may help explain why colon cancer strikes people less often in regions of the world where disease-causing E. coli infections are more common. The finding also suggests promising new directions for treating the cancer.

Each year, about 150,000 people are diagnosed with colon cancer in the United States alone. Although the disease is the fourth-leading cause of cancer-related mortality worldwide, few people living in developing nations contract the illness. That led clinical pharmacologists Giovanni M. Pitari and Scott A. Waldman of Thomas Jefferson University in Philadelphia to suspect environmental factors.

Infectious strains of E. coli lurk in the water and food in many developing regions in Africa, South America, and elsewhere. The bacteria-produced enterotoxin interacts with intestinal cells to spur diarrhea. Pitari and Waldman wondered whether enterotoxin might also stunt the proliferation of cells in the intestine, thereby protecting against cancer there.

To find out, the researchers provided a synthetic version of enterotoxin to human colon cancer cells growing in lab dishes. In a forthcoming Proceedings of the National Academy of Sciences, they report that this treatment halved the rate of cell proliferation.

In their experiments, Pitari and Waldman also observed that the toxin's stifling of cell division depends on a cascade of molecular events culminating with an influx of calcium into the cells. That result jibes with research suggesting that dietary calcium can thwart colon cancer. The team is now planning animal studies to test the toxin's cancer-fighting potential.

If those experiments pan out, the toxin could become the basis of new treatments for colon cancer, the researchers say. Enterotoxin's penchant for intestinal cells indicates that as a drug, it would focus on just those cells and leave others alone. If injected into the blood, it might even specifically combat colon cancer cells that had migrated to other parts of the body, thereby derailing metastasis, a serious problem in this cancer. Pitari and Waldman predict that such a drug would have few, if any, side effects except for diarrhea.

"That's not a bad tradeoff," remarks infectious disease expert Stephen L. Carrithers of the University of Kentucky Markey Cancer Center in Lexington. Molecular biologist Ferid Murad of the University of Texas at Houston says the finding will spark "lots of ideas" for the treatment of colon cancer.

"What's really cool," adds oncologist Mark J. Ratain of the University of Chicago Hospital, is that the trail to enterotoxin's anticancer potential originated from the global pattern of the incidence of colon cancer, not from a detailed understanding of cancer biology.