Screening of natural compounds for epigenetic regulation via DNMT1 suppression

Abstract

Epigenetic alteration is considered a crucial factor contributing to the development of various chronic diseases such as cancer, aging, and metabolic disorders. While dysregulated epigenetic modifications can exacerbate diseases, their reversible properties make them attractive targets for drug development. Natural compounds offer an invaluable resource for drug discovery. In contrast to synthetic chemicals, they are often less toxic, more biocompatible and pleiotropic, affecting multiple targets. In this context, we focused on identifying novel natural compounds that act as epigenetic modulators. We screened 46 natural compounds to determine the ability to deplete DNA methyltransferase 1 (DNMT1) expression. Five promising compounds decreased the protein level of DNMT1 in a dose-dependent manner. It suggests these compounds may be associated with DNA methylation through interactions with DNMT1 and other linked epigenetic factors. Further studies are needed to understand how these compounds regulate DNMT1 protein expression. These natural compounds have the potential to reverse abnormal epigenetic marks, re-activate silenced genes, and restore normal cellular functions.