Cancer Research Lab

Superoxide produced by Enterococcus faecalis promotes chromosomal instability in hamster cells in vitro, according to a report in the February issue of Gastroenterology.

“I like to think of our project as the colonic variation of the Helicobacter pylori and gastric cancer story,” Dr. Mark M. Huycke from University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma said. “We hypothesize that commensal bacteria play a significant role in generating chromosomal instability by abnormally activating colonic macrophages and that this leads to sporadic colorectal cancer through a bystander effect.

Dr. Huycke and Dr. Xingmin Wang investigated whether E. faecalis, which produces extracellular superoxide, could promote chromosomal instability in hybrid hamster cells containing human chromosome 11.

The fraction of hamster cells bearing mutations increased in a dose dependent manner in the presence of E. faecalis, the researchers report, whereas E. coli did not.

E. faecalis induced chromosomal instability by way of extracellular superoxide-mediated cyclooxygenase (COX)-2 expression, the results indicated.

The process involved macrophages that generated COX-2 in response to superoxide and produced diffusible mediators that promoted chromosomal instability in neighboring cells through a bystander effect, the researchers note.

“In this scenario, sporadic colorectal cancer is a disease of innate immunity produced by a specific bacterial trigger,” Dr. Huycke said. “We selected E. faecalis to test this theory because of its unusual redox properties, but have no reason to doubt that other bacteria might not also trigger macrophages to induce a bystander effect.”

“Understanding the role of commensal bacteria in the etiology of colon cancer will open new avenues for pharmaceutical intervention and, potentially, suggest preventive strategies using probiotics,” Dr. Huycke concluded.

These findings “provide further evidence for the importance of colonic microflora in colon carcinogenesis,” writes Dr. Frank A. Sinicrope from Mayo Clinic and Mayo College of Medicine, Rochester, Minnesota in a related editorial. “Studies to replicate these provocative data in an in vivo model are eagerly awaited and have the potential to further our understanding of colon carcinogenesis and also to influence strategies for colorectal cancer prevention.”