Cargando…

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

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 aim...

Descripción completa

Detalles Bibliográficos
Autores principales: Bouyahya, Abdelhakim, Mechchate, Hamza, Oumeslakht, Loubna, Zeouk, Ikrame, Aboulaghras, Sara, Balahbib, Abdelaali, Zengin, Gokhan, Kamal, Mohammad Amjad, Gallo, Monica, Montesano, Domenico, El Omari, Nasreddine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945214/
https://www.ncbi.nlm.nih.gov/pubmed/35327559
http://dx.doi.org/10.3390/biom12030367
_version_ 1784673906353766400
author Bouyahya, Abdelhakim
Mechchate, Hamza
Oumeslakht, Loubna
Zeouk, Ikrame
Aboulaghras, Sara
Balahbib, Abdelaali
Zengin, Gokhan
Kamal, Mohammad Amjad
Gallo, Monica
Montesano, Domenico
El Omari, Nasreddine
author_facet Bouyahya, Abdelhakim
Mechchate, Hamza
Oumeslakht, Loubna
Zeouk, Ikrame
Aboulaghras, Sara
Balahbib, Abdelaali
Zengin, Gokhan
Kamal, Mohammad Amjad
Gallo, Monica
Montesano, Domenico
El Omari, Nasreddine
author_sort Bouyahya, Abdelhakim
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8945214
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89452142022-03-25 The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions Bouyahya, Abdelhakim Mechchate, Hamza Oumeslakht, Loubna Zeouk, Ikrame Aboulaghras, Sara Balahbib, Abdelaali Zengin, Gokhan Kamal, Mohammad Amjad Gallo, Monica Montesano, Domenico El Omari, Nasreddine Biomolecules Review 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. MDPI 2022-02-25 /pmc/articles/PMC8945214/ /pubmed/35327559 http://dx.doi.org/10.3390/biom12030367 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bouyahya, Abdelhakim
Mechchate, Hamza
Oumeslakht, Loubna
Zeouk, Ikrame
Aboulaghras, Sara
Balahbib, Abdelaali
Zengin, Gokhan
Kamal, Mohammad Amjad
Gallo, Monica
Montesano, Domenico
El Omari, Nasreddine
The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions
title The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions
title_full The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions
title_fullStr The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions
title_full_unstemmed The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions
title_short The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions
title_sort role of epigenetic modifications in human cancers and the use of natural compounds as epidrugs: mechanistic pathways and pharmacodynamic actions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945214/
https://www.ncbi.nlm.nih.gov/pubmed/35327559
http://dx.doi.org/10.3390/biom12030367
work_keys_str_mv AT bouyahyaabdelhakim theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT mechchatehamza theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT oumeslakhtloubna theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT zeoukikrame theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT aboulaghrassara theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT balahbibabdelaali theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT zengingokhan theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT kamalmohammadamjad theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT gallomonica theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT montesanodomenico theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT elomarinasreddine theroleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT bouyahyaabdelhakim roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT mechchatehamza roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT oumeslakhtloubna roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT zeoukikrame roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT aboulaghrassara roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT balahbibabdelaali roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT zengingokhan roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT kamalmohammadamjad roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT gallomonica roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT montesanodomenico roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions
AT elomarinasreddine roleofepigeneticmodificationsinhumancancersandtheuseofnaturalcompoundsasepidrugsmechanisticpathwaysandpharmacodynamicactions