Alhosin et al. Journal of Experimental & Clinical Cancer Research 2011, 30:41 http://www.jeccr.com/content/30/1/41 R E V I E W Open Access Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties Mahmoud Alhosin, Tanveer Sharif, Marc Mousli, Nelly Etienne-Selloum, Guy Fuhrmann, Valérie B Schini-Kerth and Christian Bronner* Abstract Over-expressed in numerous cancers, Ubiquitin-like containing PHD Ring Finger 1 (UHRF1, also known as ICBP90 or Np95) is characterized by a SRA domain (Set and Ring Associated) which is found only in the UHRF family. UHRF1 constitutes a complex with histone deacetylase 1 (HDAC1) and DNA methyltransferase 1 (DNMT1) via its SRA domain and represses the expression of several tumour suppressor genes (TSGs) including p16INK4A, hMLH1, BRCA1 and RB1. Conversely, UHRF1 is regulated by other TSGs such as p53 and p73. UHRF1 is hypothetically involved in a macro-molecular protein complex called “ECREM” for “Epigenetic Code Replication Machinery”. This complex would be able to duplicate the epigenetic code by acting at the DNA replication fork and by activating the right enzymatic activity at the right moment. There are increasing evidence that UHRF1 is the conductor of this replication process by ensuring the crosstalk between DNA methylation and histone modifications via the SRA and Tandem Tudor Domains, respectively. This cross-talk allows cancer cells to maintain the repression of TSGs during cell proliferation. Several studies showed that down-regulation of UHRF1 expression in cancer cells by natural pharmacological active compounds, favors enhanced expression or re-expression of TSGs, suppresses cell growth and induces apoptosis. This suggests that hindering UHRF1 to exert its role in the duplication of the methylation patterns (DNA + histones) is responsible for inducing apoptosis. In this review, we present UHRF1 expression as a target of several natural products and we discuss their underlying molecular mechanisms and benefits for chemoprevention and chemotherapy. 1. Introduction Cancer is one of the main causes of death among Wes- ternized countries and is principally due to environmen- tal risk factors, including diet [1]. It is caused by a series of genetic and epigenetic abnormalities that induce the activation of oncogenes and/or the inactivation of tumour suppressor genes (TSGs) [2,3]. For instance, col- orectal cancer is known to be a consequence of succes- sive genetic and epigenetic changes [4,5]. Indeed, an aberrant promoter hypermethylation of the hMLH1 gene (Human Mutant L homologue 1) is a potential major cause of colon carcinogenesis suggesting that an * Correspondence: christian.bronner@unistra.fr CNRS UMR 7213 Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, Faculté de Pharmacie, 74 route du Rhin, 67401 Illkirch, France epigenetic mechanism is underlying tumorogenesis [6]. The term epigenetic is defined as heritable modification in gene expression without any variation in the DNA sequence [2,3,7,8]. DNA methylation and histone post- translational changes are the two main hallmarks of the epigenetic process. Unlike the genetic abnormalities which are irreversible, epigenetic alterations could be reversible making them as interesting therapeutic tar- gets. Epigenetic regulation of gene expression is particu- larly sensitive to environmental conditions, including diet [9]. A few examples clearly demonstrate that dietary behaviours can affect the future health of subsequent generations, by increasing the risk of cardio-metabolic diseases such as diabetes mellitus, hypertension and obesity [9]. © 2011 Alhosin et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.