Phytochemicals in cancer prevention: modulating epigenetic alterations of DNA methylation

Abstract

Cancer can take many years to develop from initiation to progression. The long period of development might represent an opportunity to use multi-functional, multi-targeted preventive drugs to block or reverse tumorigenesis. One path to cancer prevention could be to target and reverse the early epigenetic alterations. Unlike genetic mutations, they are potentially reversible and can be restored to their normal state. Epidemiological studies have revealed the close link between rich diets in bioactive compounds and the low incidence of different types of cancer. Thus, the study regarding the impact of bioactive nutrients on the epigenome has become widespread, with focus on the modulation of epigenetic mechanisms of gene expression, such as genomic DNA methylation. Following altered activity and expression of DNA methyl transferases and ten-eleven translocation enzymes, different types of cancers exert local DNA hypermethylation of gene promoters of tumor suppressor genes or of non-coding RNAs (microRNAs and long-noncoding RNAs), as well as global hypomethylation. Recently, the potential of phytochemicals to modulate epigenetic events in human health has become evident, although specific molecular mechanisms are still unclear. Phytochemicals and other bioactive dietary compounds can restore global and gene-specific promoter DNA methylation patterns by reactivating DNA methyltransferases or by providing the provision of methyl groups. Several natural products, such as EGCG, curcumin, sulforaphane, have shown DNMT inhibitory activity, but this property needs more in-depth investigations. This review focuses on the impact of modified DNA methylation pattern on early carcinogenesis and summarizes the effects/mechanism of phytochemical interventions on this type of epigenetic alterations.

Rapha Myr®, a Blend of Sulforaphane and Myrosinase, Exerts Antitumor and Anoikis-Sensitizing Effects on Human Astrocytoma Cells Modulating Sirtuins and DNA Methylation

“…Rapha Myr ® induces the upregulation of DNA methyltransferase1 (DNMT1) mRNA level and global DNA hypermethylation, unlike the results from other authors reporting that SFN induces DNA hypomethylation and decreased levels of DNMT1 in several types of cancer cells (breast, prostate, colon and liver) [ 55 ]. Among epigenetic markers, the sirtuins, a family of NAD + −dependent histone deacetylases comprising seven proteins from Sirt1 to Sirt7, are involved in many crucial cellular processes [ 56 , 57 ].…”

Diet-Epigenome Interactions: Epi-Drugs Modulating the Epigenetic Machinery during Cancer Prevention

“…As known, epigenetic modifications of chromatin are reversible and inherited, so they represent promising targets for the development of novel drugs targeting the epigenome which can contribute to amelioration of conventional therapies in cancer [44]. It has been reported that a diet rich in phytochemicals may act through epigenetic mechanisms such as modulation of DNMTs and HDACs activities that can significantly reduce the risk of cancer development by regulating the expression of oncogenes and tumor suppressor genes [45]. Cancer treatments are involved using chemo-radio therapeutic agents, kinase inhibitors, antibodies as well as certain compounds that stimulate the immune system, generally.…”

“…Cancer treatments are involved using chemo-radio therapeutic agents, kinase inhibitors, antibodies as well as certain compounds that stimulate the immune system, generally. Meanwhile, demethylating drugs modified gene expressions by reversing the aberrant epigenetic alterations acquired during tumorigenesis [44,45]. In this context, polyphenolic flavonoid compounds may represent an alternative therapeutic option for cancer treatment.…”

“…on early carcinogenesis and summarizes the effects/mechanism of phytochemical interventions on this type of epigenetic alterations. Recent investigations reported that flavonoids blocked the development and progression of tumors by targeting key signaling transducers resulting in the restoration of tumor suppressor genes, and inhibition of oncogenes expression [44][45][46][47] by modulating epigenetic machinery that is included the regulation of DNMTs and HDACs activities (Figure 8) [27].…”

Recent Advances on Graphene Quantum Dots as Multifunctional Nanoplatforms for Cancer Treatment

“…[ 2 ] Cancer pathologies are multistep processes resulting from the interplay of genetics and epigenetics alterations as well as from environmental and lifestyle factors. [ 3 ] Among the most widely used treatments to fight these pathologies, such as surgery, radiation, chemo‐ and hormonal treatments, chemotherapy is considered the most effective and extensively used method in most types of cancers. Nevertheless, the current therapeutic regimes are often limited by the systemic toxicity of anticancer drugs, mainly due to the lack of selectivity for cancer cells and tissues, the development of drug‐resistant cancer cells, and to the hydrophobic nature of many anticancer drugs which often leads to a poor cell distribution.…”