The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions

Abstract

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.

The Antioxidant, Analgesic, Anti-Inflammatory, and Wound Healing Activities of Haplophyllum tuberculatum (Forsskal) A. Juss Aqueous and Ethanolic Extract

“…This is the first study to report the healing activity of H. tuberculatum extracts. According to the results obtained, and those found in the bibliography, we can suggest that the composition of the aqueous extract of H. tuberculatum in polyphenols, especially flavonoids, gives it a healing potential [ 34 , 35 ].…”

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

“…Amentoflavone is a biflavonoid found in many plants, such as Ginkgo biloba , Chamaecyparis obtusa , Xerophyta plicata, etc. [ 63 ]. It was reported that amentoflavone can reduce cell viability and induce apoptosis in glioma cell lines in a dose-dependent manner [ 64 ].…”

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

“…Epigenetic perturbations are widespread in cancer and can be used as biomarkers to assess prognosis and treatment response [ 150 ]. Epigenetic reprogramming represents a potential therapeutic target in cancer by downregulating the transcription of genes associated with tumor invasion and upregulating genes that are abnormally silenced in cancer cells [ 151 , 152 ].…”