An active ingredient in red-hot chili peppers, called capsaicin, has been found to reduce the risk of colorectal tumors in mice.

When capsaicin is fed to mice, it produces a chronic activation of a receptor present on the cells lining their intestines, which in turn triggers a reaction that greatly reduces intestinal tumors and increases their lifespans. This study can be used to develop therapeutics that will reduce the intensity of colorectal cancer in humans. The research, carried out by scientists at the University of California, San Diego, School of Medicine appears in The Journal of Clinical Investigation.

The receptor or ion channel, called transient receptor potential vanilloid receptor (TRPV1), plays a central role in initiating inflammatory processes and painful stimuli. Originally discovered in sensory neurons, it controls our pain reactions to environmental stimuli such as heat, acidity, and spicy chemicals. "These are all potentially harmful stimuli to cells," said Dr. Eyal Raz, professor of Medicine and senior author of the study. "Thus, TRPV1 was quickly described as a molecular 'pain receptor.' This can be considered to be its conventional function, which all takes place in the nervous system."

But Raz and his team discovered that TRPV1 is also expressed by epithelial cells of the intestines where it is activated by epidermal growth factor receptor or EGFR. EGFR is a cell surface protein that binds to epidermal growth factor and causes proliferation of the epithelial cells in the intestine. This epithelial lining gets replaced every four to six days. Mutation in this receptor causes cancer.

"A basic level of EGFR activity is required to maintain the normal cell turnover in the gut," said Dr. Petrus de Jong, first author of the study. "However, if EGFR signaling is left unrestrained, the risk of sporadic tumor development increases."

The scientists discovered that TRPV1, once activated by the EGFR, initiates a direct negative feedback on the EGFR, dampening the latter to reduce the risk of unwanted growth and intestinal tumor development. Mice, who had been genetically modified to be TRPV1-deficient, became susceptible to more intestinal tumor growth than normal.

"These results showed us that epithelial TRPV1 normally works as a tumor suppressor in the intestines," de Jong said. Recent molecular studies of human colorectal cancer samples have also shown multiple mutations in the TRPV1 gene. But currently it has not been proven that TRPV1 deficiency results in colorectal cancer risk in humans according to Raz. "A direct association between TRPV1 function and human colorectal cancer should be addressed in future clinical studies," he said.

If TRPV1 does indeed cause cancer, then a therapeutic solution to curb it would be spicy capsaicin. Found in chili peppers, it acts as an irritant in mammals and produces a burning sensation in any tissue it comes in contact with. It is already being widely used as an analgesic in topical ointments. Capsaicin’s anti-inflammatory effect occurs because the burning sensation it produces renders the nerves incapable of reporting pain for long periods of time. Prolonged exposure to capsaicin causes the neurotransmitters from the neurons to be depleted, leading to reduction in pain sensation. 

When the researchers fed mice genetically induced to develop multiple tumors in the gut with capsaicin, they found a reduction in the number of tumors. Their general life also increased by more than 30 percent. The treatment was even more effective when combined with celecoxib, a COX-2 non-steroidal anti-inflammatory drug already approved for treating some forms of arthritis and pain.

"Our data suggest that individuals at high risk of developing recurrent intestinal tumors may benefit from chronic TRPV1 activation," said Raz in a statement. "We have provided proof-of-principle." 

Source: Raz, E, Takahashi N, Harris A, et al. The Journal of Clinical Investigation. 2014.