Natural compounds: Role in reversal of epigenetic changes

Abstract

The hallmarks of carcinogenesis are characterized by alterations in the expression of multiple genes that occur via genetic and epigenetic alterations, leading to genome rearrangements and instability. The reversible process of epigenetic regulation, which includes changes in DNA methylation, histone modifications, and alteration in microRNA (miRNA) expression that alter phenotype without any change in the DNA sequence, is recognized as a key mechanism in cancer cell metabolism. Recent advancements in the rapidly evolving field of cancer epigenetics have shown the anticarcinogenic potential of natural compounds targeting epigenetic mechanism as a common molecular approach for cancer treatment. This review summarizes the potential of natural chemopreventive agents to reverse cancer-related epigenetic aberrations by regulating the activity of histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs. Furthermore, there is impetus for determining novel and effective chemopreventive strategies, either alone or in combination with other anticancer agents that exhibit similar properties, for improving the therapeutic aspects of cancer.

Natural Products for the Management and Prevention of Breast Cancer

“…Accumulating evidences showed that natural phytochemicals including the secondary metabolites found in the dietary foods have the ability to modulate the epigenetic events and reverse the epigenetic changes before causing cancer progression [ 54 , 55 ]. By targeting specific key transcription factors, kinases, and growth factor receptor mediated pathways, phytochemicals are reported to exert their actions in epigenetic alterations through cell cycle arrest, initiating apoptosis and reactivation of tumor suppressing genes [ 56 , 57 ]. In breast cancer chemoprevention, the article reported by Chlebowski [ 58 ] showed the effective chemopreventive actions of tamoxifen and some aromatase inhibitors including exemestane and anastrozole in reduction of breast cancer on clinical trial studies.…”

New Insights into the Epigenetic Activities of Natural Compounds

“…In silico, curcumin binds the DNMT1 catalytic site ( Figure S2). The major isoflavones from soybean, genistein, and biochanin A, have also been reported to have DNA demethylating activity [1][2][3][4]. Although their mechanisms of action remain to be fully elucidated, in this study, we show that S-equol, an isoflavone metabolite, remains a strong DNA demethylating agent.…”

“…Several natural nutrients have been found to affect the epigenome through modification of DNA and histone methylation and histone acetylation as well as modifications of micro and long non-coding RNAs. We previously reported that several dietary polyphenols that are well-known as in vitro anti-oxidants are also documented epigenetic modifiers [1,2]; however, conflicting results were obtained [1][2][3][4]. Recent evidence supports a reduction in mortality risk associated with a polyphenol-rich diet [5].…”

Targeting DNA Methyltranferases in Urological Tumors

“…Their ability to interact with several protein families hinder the precise characterization of its anti-neoplastic effects, making it difficult to discriminate whether these result from direct modulation of one or more epigenetic targets. This unspecific mode of action might culminate in activation of unwanted pathways that may favor tumor growth and progression (Miceli et al, 2014 ; Aggarwal et al, 2015 ). In an attempt to overcome this, chemical probes have been progressively highlighted in recent years as valuable small-molecules to investigate complex biological mechanisms and processes related with disease onset, including cancer.…”