Thymoquinone Is a Multitarget Single Epidrug That Inhibits the UHRF1 Protein Complex.
Fiche publication
Date publication
avril 2021
Journal
Genes
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRONNER Christian, Dr HAMICHE Ali
Tous les auteurs :
Abdullah O, Omran Z, Hosawi S, Hamiche A, Bronner C, Alhosin M
Lien Pubmed
Résumé
Silencing of tumor suppressor genes (TSGs) through epigenetic mechanisms, mainly via abnormal promoter DNA methylation, is considered a main mechanism of tumorigenesis. The abnormal DNA methylation profiles are transmitted from the cancer mother cell to the daughter cells through the involvement of a macromolecular complex in which the ubiquitin-like containing plant homeodomain (PHD), and an interesting new gene (RING) finger domains 1 (UHRF1), play the role of conductor. Indeed, UHRF1 interacts with epigenetic writers, such as DNA methyltransferase 1 (DNMT1), histone methyltransferase G9a, erasers like histone deacetylase 1 (HDAC1), and functions as a hub protein. Thus, targeting UHRF1 and/or its partners is a promising strategy for epigenetic cancer therapy. The natural compound thymoquinone (TQ) exhibits anticancer activities by targeting several cellular signaling pathways, including those involving UHRF1. In this review, we highlight TQ as a potential multitarget single epidrug that functions by targeting the UHRF1/DNMT1/HDAC1/G9a complex. We also speculate on the possibility that TQ might specifically target UHRF1, with subsequent regulatory effects on other partners.
Mots clés
UHRF1, cancer, epigenetic drug, thymoquinone, tumor suppressor gene
Référence
Genes (Basel). 2021 Apr 22;12(5):