UC San Diego School of Medicine researchers have been studying chili peppers. Not at the local Mexican restaurant, but in the lab. The mouth-burning intestine-burning natural food may hold the key to a major health problem. Peppers contain capsaicin, which produces chronic activation of a receptor on cells that line the intestines of mice. That activation appears to trigger a reaction that ultimately reduces the risk of colorectal tumors.
The findings are published in the August 1, 2014 issue of The Journal of Clinical Investigation.
TRPV1, the receptor or ion channel, originally discovered in sensory neurons, acts as a sentinel for heat, acidity and spicy chemicals in the environment.
As we know, heat, acidity and spicy chemicals are dangerous to us. Eyal Raz, MD, professor of Medicine and senior author of the study said all three of these things are “potentially harmful stimuli to cells.” So this means that TRPV1 is a molecular pain receptor. Raz and his colleagues say TRPV1’s conventional function is in the nervous system, but it has other functions.
A release about this effect says:
TPRV1 is also expressed by epithelial cells of the intestines, where it is activated by epidermal growth factor receptor (EGFR). This receptor is an important driver of cell proliferation in the intestines, whose epithelial lining is replaced approximately every four to six days.
Petrus de Jong, MD, first author of the study says some level of epidermal growth factor receptor activity “is required to maintain the normal cell turnover in the gut,” but there is a possible negative effect too. “If EGFR signaling is left unrestrained, the risk of sporadic tumor development increases.”
Feedback Loop
Once activated by the EGFR, the scientists discovered that TRPV1 initiates “a direct negative feedback on the EGFR, dampening the latter to reduce the risk of unwanted growth and intestinal tumor development.” They tested mice that had been genetically modified to be TRPV1-deficient. Those mice suffered from higher than normal rates of intestinal tumor growths.
De Jong says this means their results show that “epithelial TRPV1 normally works as a tumor suppressor in the intestines.”
The scientists looked at molecular studies of human colorectal cancer samples. Those studies show multiple mutations in the TRPV1 gene, but Raz says they need to undertake more studies, because there is currently no direct evidence that TRPV1 deficiency is a risk factor for colorectal cancer in humans.
It is already known that capsaicin is an irritant, hence its use in pepper spray and ointments. Used in topical ointments, capsaicin acts as an analgesic irritant that overwhelms nerves, rendering them unable to report pain for extended periods.
The researchers provided a proof-of-principle that people who are at high risk of developing recurrent intestinal tumors may benefit from chronic TRPV1 activation.
This was done by feeding capsaicin to the mice that were genetically prone to developing multiple tumors in the gastrointestinal tract. The result of their test treatment was lower numbers of tumours and additional life extension of around 30 percent. In other tests, they combined the capsaicin with celecoxib, a COX-2 non-steroidal anti-inflammatory drug. The combination was even more effective than capsaicin alone. Celecoxib is already approved for treating some forms of arthritis and pain.
The Research Team
Here is what the release says about the research team and their funding.
Co-authors include Petrus R. de Jong, UCSD Department of Medicine and University Medical Center Utrecht, The Netherlands; Naoki Takahashi, UCSD Department of Medicine and Niigata University Graduate School of Medical and Dental Sciences, Japan; Alexandra R. Harris, Jihyung Lee, Samuel Bertin, James Jeffries, Michael Jung, Jen Duong, Amy I. Triano, Jongdae Lee, David S. Herdman, Hui Dong, Lars Eckmann and Maripat Corr, UCSD Department of Medicine; Yaron Niv, Rabin Medical Center and Tel Aviv University, Israel; Koji Taniguchi, UCSD Department of Medicine and Keio University School of Medicine, Japan; Chang-Whan Kim, UCSD Department of Medicine and Catholic University of Korea; Stephanie M Stanford and Nunzio Bottini, La Jolla Institute for Allergy and Immunology.
This research was supported, in part, by the Crohn’s and Colitis Foundation of America, the Prins Bernhard Cultural Foundation, the Scholten-Cordes Foundation, the Dr. Hendrick Muller Vaderlandsch Foundation, the Japan Society for the Promotion of Science, the European Molecular Biology Organization, the Juvenile Diabetes Research Foundation, the Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation, the Broad Medical Foundation and the National Institutes of Health (grants AI095623 and DK35108).
