Urolithin A: A promising selective estrogen receptor modulator and 27-hydroxycholesterol attenuator in breast cancer.
27-hydroxycholesterol (27-HC)
breast cancer
selective estrogen receptor modulator (SERM)
urolithin A
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
08
05
2023
received:
04
11
2022
accepted:
27
05
2023
pubmed:
22
6
2023
medline:
22
6
2023
entrez:
22
6
2023
Statut:
ppublish
Résumé
27-hydroxycholesterol (27-HC) is an oxysterol that acts as an endogenous selective estrogen receptor modulator (SERM), and its adverse effects on breast cancer via the estrogen receptor (ER) have provided new insights into the pathology of cholesterol-linked breast cancer. Our earlier in vitro experiments showed that the methanolic extract of pomegranate could exhibit SERM properties and compete with 27-HC. The major constituents of pomegranate are ellagitannins and ellagic acid, which are converted into urolithins by the colonic microbiota. In recent years, urolithins, especially urolithin A (UA) and urolithin B (UB), have been reported to have a plethora of advantageous effects, including antiproliferative and estrogenic activities. In this study, we attempted to determine the potential of urolithins in antagonizing and counteracting the adverse effects of 27-HC in breast cancer cells. Our findings suggested that UA had an antiproliferative capacity and attenuated the proliferative effects of 27-HC, resulting in subsequent loss of membrane potential and apoptosis in breast cancer cells. Further, UA induced estrogen response element (ERE) transcriptional activity and modulated estrogen-responsive genes, exhibiting a SERM-like response concerning receptor binding. Our in vivo hollow fiber assay results showed a loss of cell viability in breast cancer cells upon UA consumption, as well as a reduction in 27-HC-induced proliferative activity. Additionally, it was shown that UA did not induce uterine proliferation or alter blood biochemical parameters. Based on these findings, we can conclude that UA has the potential to act as a potent estrogen receptor alpha (ERα) modulator and 27-HC antagonist. UA is safe to consume and is very well tolerated. This study further opens up the potential of UA as ER modulator and its benefits in estrogen-dependent tissues.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4504-4521Subventions
Organisme : Science and Engineering Research Board
ID : EMR/000557
Organisme : Department of Biotechnology
ID : BT/01/CEIB/01/CB/2016
Informations de copyright
© 2023 John Wiley & Sons Ltd.
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