Natural compound-derived epigenetic regulators targeting epigenetic readers, writers and erasers

Abstract

Post-translational modifications can affect gene expression in a long-term manner without changes in the primary nucleotide sequence of the DNA. These epigenetic alterations involve dynamic processes that occur in histones, chromatin-associated proteins and DNA. In response to environmental stimuli, abnormal epigenetic alterations cause disorders in the cell cycle, apoptosis and other cellular processes and thus contribute to the incidence of diverse diseases, including cancers. In this review, we will summarize recent studies focusing on certain epigenetic readers, writers, and erasers associated with cancer development and how newly discovered natural compounds and their derivatives could interact with these targets. These advances provide insights into epigenetic alterations in cancers and the potential utility of these alterations as therapeutic targets for the future development of chemopreventive and chemotherapeutic drugs.

Fucoxanthin Elicits Epigenetic Modifications, Nrf2 Activation and Blocking Transformation in Mouse Skin JB6 P+ Cells

“…Aberrant epigenetic alterations have been observed in the initiation and progression of skin cancers (14–17). Certain dietary phytochemicals that possess chemopreventive effects have been reported to prevent cancer by targeting epigenetic modifications (18, 19). For example, sulforaphane and phenethyl isothiocyanate, which are derived from cruciferous vegetables and allyl compounds in garlic, have been reported to be potent inhibitors of HDACs and DNMTs (20–24).…”

DNA Tandem Repeats as Iterable Objects to Count Cell Divisions: A Computational Model

“…SatDNA is actively methylated [21] and plays an important role in epigenetics [22] [23] [24]; epigenetic tools comprise specialized enzymes [25] able to recognize the particular 3D structure of their target sequences: "writers" [26] catalyze biochemical modifications (e.g. DNA methyltransferases: methylation on the 5th position of the pyrimidine ring of cytosine, C ↠ 5mC), "readers" [27] recognize and interpret the significance of such modifications and recruit a set of methyl CpG-binding proteins and "erasers" [28] remove methylations [29] [30] [31]. Hypomethylated TR arrays have been found in different human diseases, cancer, and psychiatric disorders [32].…”

Novel epigenetic therapeutic strategies and targets in cancer

“…These two changes commonly influence cellular gene expression patterns by switching between transcriptional activation and suppression [99]. Histone methyltransferases (HMTs, including histone lysine methyltransferases and protein arginine methyltransferases), histone acetyltransferases (HATs) and DNMTs are all remarkable examples of writer proteins [100], with DNMTs being the most attractive targets for therapeutic research, and clinical studies are underway for a number of inhibitors like azacytidine and decitabin to target these proteins [9,101].…”