Epigenetic Alterations in Ultraviolet Radiation‐Induced Skin Carcinogenesis: Interaction of Bioactive Dietary Components on Epigenetic Targets^†

Abstract

The importance of epigenetic alterations in the development of various diseases including the cancers has been realized. As epigenetic changes are reversible heritable changes, these can be utilized as an effective strategy for the prevention of cancers. DNA methylation is the most characterized epigenetic mechanism that can be inherited without changing the DNA sequence. Although limited, but available data suggest that silencing of tumor suppressor genes in ultraviolet (UV) radiation-exposed epidermis leads to photocarcinogenesis and is associated with a network of epigenetic modifications including alterations in DNA methylation, DNA methyltransferases and histone acetylations. Various bioactive dietary components have been shown to protect skin from UV radiation-induced skin tumors in animal models. The role of bioactive dietary components, such as, (−)-epicatechins from green tea and proanthocyanidins from grape seeds, has been assessed in chemoprevention of UV-induced skin carcinogenesis and underlying epigenetic mechanism in vitro and in vivo animal models. These bioactive components have the ability to block UV-induced DNA hypermethylation and histone modifications in the skin required for the silencing of tumor suppressor genes (e.g., Cip1/p21, p16INK4a). These information are of importance for understanding the role of epigenetic modulation in UV-induced skin tumor and the chemopreventive mechanism of bioactive dietary components.

New Frontiers in Melanoma Epigenetics—The More We Know, the More We Don’t Know

“…Similar results were obtained on mice exposed to UV light, where DNA hypomethylation patches were observed [15,20].…”

“…Some results suggest that UVB radiation might induce not only TP53 mutations, but also alterations of methylation in keratinocytes and other skin cell types at a relatively early stage in areas of human skin which were chronically exposed to sunlight [15]. Similar results were obtained on mice exposed to UV light, where DNA hypomethylation patches were observed [15,20].…”

“…Worthwhile studies by Katiyar et al have also shown a connection between regional DNA hypermethylation and hypoacetylation of histones with downregulation of several tumour suppressor genes [15]. Especially, UV-induced hypoacetylation of histones H3 and H4 in the transcriptionally-silenced tumour-suppressor genes RASSF1A and p16 INKa was discovered.…”

“…Skin exposure to this radiation induces DNA damage, oxidative stress, inflammatory responses and sometimes suppression of immune reactions, all of which may significantly change epigenetic status, especially DNA methylation and modifications of histone proteins [15]. It has been noted that chronic inflammation itself may lead to acquisition of epigenetic alterations [16].…”

Reserpine Inhibit the JB6 P+ Cell Transformation Through Epigenetic Reactivation of Nrf2-Mediated Anti-oxidative Stress Pathway

“…However, the severe toxic effects and lack of gene specificity limit the application of these drugs. However, phytochemicals with DNA methylation-modulating properties are promising alternatives for cancer chemoprevention, as these compounds have minor side effects (29,30). In this study, we examined the anticancer effect of reserpine on a JB6 P+ cell transformation model and the epigenetic reactivation of the Nrf2 signaling pathway.…”