A recent study from the University of California, San Diego School of Medicine (CA, USA) has reported that dietary capsaicin, the active ingredient in chilli peppers, can potentially reduce the risk of colorectal tumors.
The TRPV1 receptor, originally found expressed in sensory neurons (where it is sensitive to heat, acidity and spicy chemicals, i.e., capsaicin) has been found to also be expressed in intestinal epithelial cells (IECs). Here, the receptor is intrinsically activated by the EGF receptor (EGFR), a key mediator of cell proliferation, which in turn led to inhibition of EGFR-induced epithelial cell proliferation through activation of Ca2+/calpain and PTP1B.
Using a murine model of multiple intestinal neoplasia (ApcMin/+ mice), the researchers discovered that TRPV1-deficient mice had increased tumor development. “These results showed us that epithelial TRPV1 normally works as a tumor suppressor in the intestines,” commented Petrus de Jong (University of California, San Diego School of Medicine), first author of the study. Treating the mice with an EGFR kinase inhibitor reversed the protumorigenic effects.
Furthermore, the team discovered that feeding the mice with a TRPV1 agonist, such as capsaicin, suppressed growth of intestinal tumors, reduced tumor burden and extended the life span of mice >30%. This was more effective when administered in conjunction with celecoxib, a COX-2 NSAID already approved for treatment of 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,” commented Eyal Raz, senior author of the study. “We have provided proof-of-principle.”
The study also implicates TRPV1 and COX-2 as potential therapeutic targets to aid in tumor prevention.
Sources: de Jong PR, Takahashi N, Harris AR et al. Ion channel TRPV1-dependent activation of PTP1B suppresses EGFR-associated intestinal tumorigenesis. J. Clin. Invest. doi:10.1172/JCI72340 (2014) [Epub ahead of print]; UC San Diego Health System press release