The Therapeutic Potential of Urolithin A for Cancer Treatment and Prevention

Curr Cancer Drug Targets. 2022;22(9):717-724. doi: 10.2174/1568009622666220602125343.

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.

Keywords: AhR antagonist; Urolithin A; cancer; ellagitannins; inflammation; polyphenols.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Coumarins* / pharmacology
  • Coumarins* / therapeutic use
  • Humans
  • Inflammation
  • Mice
  • Neoplasms* / drug therapy
  • Neoplasms* / prevention & control
  • Polyphenols / metabolism
  • Rats

Substances

  • Anti-Inflammatory Agents
  • Coumarins
  • Polyphenols
  • 3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one