Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1
Waseem Ashraf,
Tanveer Ahmad,
Nicolas Reynoird,
Ali Hamiche,
Yves Mély,
Christian Bronner,
Marc Mousli
Affiliations
Waseem Ashraf
Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan
Tanveer Ahmad
Institut Pour L’avancée des Biosciences, Centre de Recherche UGA, INSERM U1209, CNRS 5309, Université Grenoble Alpes, 38058 Grenoble, France
Nicolas Reynoird
Institut Pour L’avancée des Biosciences, Centre de Recherche UGA, INSERM U1209, CNRS 5309, Université Grenoble Alpes, 38058 Grenoble, France
Ali Hamiche
Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR 7104, Université de Strasbourg, Equipe Labellisée Ligue Contre le Cancer, 67401 Illkirch, France
Yves Mély
Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France
Christian Bronner
Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U1258, CNRS UMR 7104, Université de Strasbourg, Equipe Labellisée Ligue Contre le Cancer, 67401 Illkirch, France
Marc Mousli
Laboratoire de Bioimagerie et Pathologies, UMR 7021 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France
Cancer is one of the leading causes of death worldwide, and its incidence and mortality are increasing each year. Improved therapeutic strategies against cancer have progressed, but remain insufficient to invert this trend. Along with several other risk factors, abnormal genetic and epigenetic regulations play a critical role in the initiation of cellular transformation, as well as tumorigenesis. The epigenetic regulator UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is a multidomain protein with oncogenic abilities overexpressed in most cancers. Through the coordination of its multiple domains and other epigenetic key players, UHRF1 regulates DNA methylation and histone modifications. This well-coordinated dialogue leads to the silencing of tumor-suppressor genes (TSGs) and facilitates tumor cells’ resistance toward anticancer drugs, ultimately promoting apoptosis escape and uncontrolled proliferation. Several studies have shown that the downregulation of UHRF1 with natural compounds in tumor cells induces the reactivation of various TSGs, inhibits cell growth, and promotes apoptosis. In this review, we discuss the underlying mechanisms and the potential of various natural and synthetic compounds that can inhibit/minimize UHRF1’s oncogenic activities and/or its expression.
