Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention

Abstract

The growing interest in cancer epigenetics is largely due to the reversible nature of epigenetic changes which tend to alter during the course of carcinogenesis. Major epigenetic changes including DNA methylation, chromatin modifications and miRNA regulation play important roles in tumorigenic process. There are several epigenetically active synthetic molecules such as DNA methyltransferase (DNMTs) and histone deacetylases (HDACs) inhibitors, which are either approved or, are under clinical trials for the treatment of various cancers. However, most of the synthetic inhibitors have shown adverse side effects, narrow in their specificity and also expensive. Hence, bioactive phytochemicals, which are widely available with lesser toxic effects, have been tested for their role in epigenetic modulatory activities in gene regulation for cancer prevention and therapy. Encouragingly, many bioactive phytochemicals potentially altered the expression of key tumor suppressor genes, tumor promoter genes and oncogenes through modulation of DNA methylation and chromatin modification in cancer. These bioactive phytochemicals either alone or in combination with other phytochemicals showed promising results against various cancers. Here, we summarize and discuss the role of some commonly investigated phytochemicals and their epigenetic targets that are of particular interest in cancer prevention and cancer therapy.

Epigenetic Impact of Bioactive Dietary Compounds in Cancer Chemoprevention

“…Accumulating evidence demonstrates aberrant DNA methylation in most human cancers, including colon, breast, lung, and oral carcinomas (Esteller 2007;Belinsky et al 2002;Supic et al 2009Supic et al , 2011a. A number of recent studies have demonstrated that dietary phytochemicals could have an important role in cancer chemoprevention by affecting DNA methylation (Shukla et al 2014). …”

“…Thus, epigenetic modifications should not be interpreted independently, but only in combination with other modifications and within a context, leading to downstream transcriptional activation or repression suppressor genes and oncogenes through modulation of DNA methylation and chromatin modification. These bioactive phytochemicals acting alone or in combination with other natural or synthetic agents showed promising results against various cancers (Shukla et al 2014;Ullah and Khan 2008).…”

Therapeutic Potential for Natural Product HDAC Inhibitors in Heart Failure

“…Indeed, synthetic HDAC inhibitors are currently approved as well as under clinical trials for the treatment of various cancers. However, most of these synthetic inhibitors have shown adverse effects and toxicities and are also cost prohibitive [17]. Together, this has led to recent interest in bioactive food compounds that regulate epigenetic marks in the control of gene expression and human health and disease.…”

Vitamin A in prevention and treatment of cancer

“…Being micronutrients and complexity in actions, the use of vitamins in cancer is not common (Barber et al 2014;Clamon 2015). However, in some non-clinical and clinical studies, the use (both individually and combindly) of vitamins for the prevention and treatment of cancers, is evident (Coulter et al 2006; Bjelakovic et al 2013a; Shukla et al 2014). Both lipo-soluble and water-soluble vitamins supplied by the organic food materials are extremely necessary for our body homeostasis (Alabdali et al 2014;Chang et al 2015).…”