Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties

Cancer is one of the main causes of death among Westernized countries and is principally due to environmental 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, colorectal cancer is known to be a consequence of successive 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 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 targets. Epigenetic regulation of gene expression is particularly 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].Concerning cancer and transgenerational epigenetic effect of diets, in terms of increased risk, no evidence has so far yet been reported. However, cancerogenesis is now recognised as being the result of profound dietary-influenced epigenetic modifications, among which hypermethylation of the promoters of several TSGs occupies a main place [3,10]. Reversing promoter methylation of silenced tumor suppressor genes represents a current challenge for anti-cancer therapy.In mammalians, DNA methylation is the most widely studied epigenetic modification. It is mediated by a family of DNA methyltransferases (DNMTs) that transfer a m