Urolithins: The Gut Based Polyphenol Metabolites of Ellagitannins in Cancer Prevention, a Review

Abstract

Cancer as a disease continues to ravage the world population without regard to sex, age, and race. Due to the growing number of cases worldwide, cancer exerts a significant negative impact on global health and the economy. Interestingly, chemotherapy has been used over the years as a therapeutic intervention against cancer. However, high cost, resistance, and toxic by-effects to treatment have overshadowed some of its benefits. In recent times, efforts have been ongoing in searching for anticancer therapeutics of plant origin, focusing on polyphenols. Urolithins are secondary polyphenol metabolites derived from the gut microbial action on ellagitannins and ellagic acid-rich foods such as pomegranate, berries, and nuts. Urolithins are emerging as a new class of anticancer compounds that can mediate their cancer-preventive activities through cell cycle arrest, aromatase inhibition, induction of apoptosis, tumor suppression, promotion of autophagy, and senescence, transcriptional regulation of oncogenes, and growth factor receptors. In this review, we discussed the growing shreds of evidence supporting these secondary phenolic metabolites' anticancer properties. Furthermore, we have pointed out some of the future directions needed to establish urolithins as anticancer agents.

High–Pressure Processing vs. Thermal Treatment: Effect on the Stability of Polyphenols in Strawberry and Apple Products

“…The potential health benefits of ETs and EA are associated with the metabolites (urolithins) produced by the human gut microbiota [ 67 , 68 ]. The biological functions attributed to urolithins comprise anti-oxidant, neuroprotective, anti-microbial, anti-inflammatory, and anticancer properties [ 67 , 69 , 70 ]. Notably, there were no differences in urolithins’ production and urinary excretion between volunteers ingesting either fresh strawberries or thermally treated puree [ 71 ].…”

Role for Plant-Derived Antioxidants in Attenuating Cancer Cachexia

“…Due to the low bioavailability and aqueous solubility of EA, it is likely that these colonic metabolites are the bioactive compounds responsible for the reported anti-inflammatory, antioxidative and anti-cancer effects of EA [ 148 ]. Urolithin A and B have reported anti-cancer effects [ 149 ] with additional benefits in skeletal muscle. Pre-treatment with urolithin A (15 μM) for 24 h attenuated TNF-α-induced inflammation and prevented activation of NF-κB signaling to protect wasting of C2C12 myotubes in vitro [ 139 ].…”

Punicalagin in Cancer Prevention—Via Signaling Pathways Targeting

“…Compared to Pug, these released phenols lack astringent properties but retain a number of interesting activities beneficial to health, including anti-cancer properties. The newest data associated with chemopreventive functions of ellagitannin derivatives have been summarized by Al-Harbi et al [ 101 ]. The authors discussed the antineoplastic impact of various urolithin types on prostate, breast, uterine, liver, colon, and bladder cancers, with respect to the modified signaling pathways.…”