Title:The Therapeutic Potential of Urolithin A for Cancer Treatment and
Prevention
Volume: 22
Issue: 9
Author(s): Vladimir S. Rogovskii*
Affiliation:
- Department of molecular pharmacology and radiobiology, Pirogov Russian National Research Medical University, Moscow, Russia
Keywords:
Urolithin A, polyphenols, inflammation, cancer, AhR antagonist, ellagitannins.
Abstract:
Background: Urolithin A is the metabolite of natural polyphenol ellagic acid and ellagitannins
generated by gut microbiota. Urolithin A is better absorbed in the gastrointestinal tract than its parent
substances. Thus, the variable effects of ellagitannin-reach food (like pomegranate fruit, walnuts,
tea, and others) on people's health might be linked with the differences in individual microbiota content.
Urolithin A possesses various anti-inflammatory and anti-cancer effects, as shown by in vivo and in
vitro studies.
Objectives: In the current review, we consider anti-inflammatory and direct anti-cancer urolithin A effects
as well as their molecular mechanisms, which might be the basement of clinical trials, estimating
urolithin A anti-cancer effects.
Conclusion: Urolithin A attenuated the pro-inflammatory factors production (IL-6, IL-1β, NOS2 and
others) in vitro studies. Oral urolithin A treatment caused prominent anti-cancer and anti-inflammatory
action in various in vivo studies, including colitis rat model, carrageenan-induced paw edema mice
model, models of pancreatic cancer, and models of obesity. The main molecular mechanisms of these
effects might be the modulation of aryl hydrocarbon receptors, which antagonism may lead to decreasing
of chronic inflammation. Other primary targets of urolithin A might be the processes of protein
phosphorylation (for instance, it decreases the phosphorylation of protein kinase B) and p53 stabilization.
Anti-inflammatory effects of urolithin A can be reached in physiologically relevant concentrations.
This might be of vital importance for preventing immune suppression associated with chronic inflammation
in cancer. Considering the favorable urolithin A safety profile, it is a promising compound for
cancer treatment and prevention.