CHILI PEPPERS CAUSE COLO RECTAL TUMORS
Researchers at the
University of California, San Diego School of Medicine report that dietary
capsaicin -- the active ingredient in chili peppers -- produces chronic
activation of a receptor on cells lining the intestines of mice, triggering 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.
The receptor or ion
channel, called TRPV1, was originally discovered in sensory neurons, where it
acts as a sentinel for heat, acidity and spicy chemicals in the environment.
"These are all potentially harmful stimuli to cells," said Eyal Raz, MD,
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 colleagues
have found that TPRV1 is also expressed by epithelial cells of the intestines,
where it is activated by epidermal growth factor receptor or EGFR. EGFR is an
important driver of 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."
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. They found that mice 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.
"A direct
association between TRPV1 function and human colorectal cancer should be
addressed in future clinical studies," he said.
But if such proves to
be the case, the current study suggests one potential remedy might be spicy
capsaicin, which acts as an irritant in mammals, generating a burning sensation
in contact with tissue. Capsaicin is already broadly used as an analgesic in
topical ointments, where its properties as an irritant overwhelm nerves,
rendering them unable to report pain for extended periods of time. It's also
the active ingredient in pepper spray.
The researchers fed
capsaicin 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. 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. "We have provided
proof-of-principle."
Comments
Post a Comment