The active ingredient is called capsaicin and it produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that reduced the risk of colorectal tumors.
The receptor, called TRPV1, was originally discovered in sensory neurons, where it acts as a sentinel for heat, acidity and spicy chemicals in the environment. The researchers determined that TRPV1 is activated by EGFR in the gut. EGFR drives cell proliferation in the intestines, whose epithelial lining is replaced approximately every four to six days.
“A basic level of EGFR activity is required to maintain the normal cell turnover in the gut,” said Petrus de Jong, MD, first author of the study. “However, if EGFR signaling is left unrestrained, the risk of sporadic tumor development increases.”
Mice who were genetically modified to be TRPV1-deficient suffered higher-than-normal rates of intestinal tumor growths.
“These results showed us that epithelial TRPV1 normally works as a tumor suppressor in the intestines,” said de Jong. In addition, molecular studies of human colorectal cancer samples recently uncovered multiple mutations in the TRPV1 gene, though Raz noted that currently there is no direct evidence that TRPV1 deficiency is a risk factor for colorectal cancer in humans.
To test the hypothesis that capsaicin affects tumor development the researchers fed the chili ingredient to mice genetically prone to developing multiple tumors in the gastrointestinal tract. The treatment resulted in a reduced tumor burden and extended the lifespans of the mice by more than 30 percent.
“Our data suggest that individuals at high risk of developing recurrent intestinal tumors may benefit from chronic TRPV1 activation,” said Raz. “We have provided proof-of-principle.”
Petrus R. de Jong, Naoki Takahashi, Alexandra R. Harris, Jihyung Lee, Samuel Bertin, James Jeffries, Michael Jung, Jen Duong, Amy I. Triano, Jongdae Lee, Yaron Niv, David S. Herdman, Koji Taniguchi, Chang-Whan Kim, Hui Dong, Lars Eckmann, Stephanie M. Stanford, Nunzio Bottini, Maripat Corr, Eyal Raz. Ion channel TRPV1-dependent activation of PTP1B suppresses EGFR-associated intestinal tumorigenesis. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI72340