Epigenetic Cancer Prevention Mechanisms in Skin Cancer

Abstract

Abstract. Epigenetics is an important emerging area for study of mechanisms of cancer prevention. In recent years, it has been realized that cancer prevention agents, derived from natural dietary sources, impact cancer cell survival by modulating epigenetic processes. In the present manuscript, we review key epigenetic regulatory mechanisms and examine the impact of sulforaphane and green tea polyphenols on these processes. We also discuss available information on the epigenetics in the context of skin cancer. These studies indicate that diet-derived chemopreventive agents modulate DNA methylation status and histone modification via multiple processes and point to additional areas for study of epigenetic mechanisms in skin cancer.

Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells

“…To date, many genes have been shown to be silenced by CpG hypermethylation within the promoter region during tumor progression. For example, in skin cancer, 14-3-3sigma (cell cycle), MGMT (DNA repair), RASSF1 (signal transduction), PTEN (apoptosis), and others have been shown to be hypermethylated [29]. Thus, discovering compounds that are able to reduce hypermethylation is an attractive strategy for the prevention of skin cancer.…”

“…HDACs remove acetyl groups from histones, mainly histone H3 and H4. This removal accelerates the formation of a compact chromatic structure, which drives the repression of transcription and causes gene silencing [28, 29]. Because HDACs such as HADC1, HDAC2, HDAC3, HDAC6, and HDC8 are overexpressed in many cancers [64], the discovery of selective HDAC inhibitors has had significant implications for cancer therapy.…”

“…Because HDACs such as HADC1, HDAC2, HDAC3, HDAC6, and HDC8 are overexpressed in many cancers [64], the discovery of selective HDAC inhibitors has had significant implications for cancer therapy. As natural HDAC inhibitors for skin cancer, EGCG and grape seed proanthocyanidins have been reported to decrease the level of HDAC1 and HDAC activity, accompanied by reduced expression and activity of DNMTs in squamous cell carcinoma [29, 37]. Recently, sulforaphane has been shown to reduce the protein levels of HDAC1-4 and 6 in human keratinocytes [65].…”

Antitumor activity of sulforaphane in mice model of skin cancer via blocking sulfatase‐2

“…Consumption of sulforaphane was linked to the inhibition of the UV‐induced inflammation and carcinogenesis . Sulforaphane has been shown to exhibit anticancer activities via several mechanisms such as inhibition of DNA methylation, reactivation of nuclear factor E2‐related factor 2 (Nrf2), inhibition of p21 and silencing of tumor promoting genes . Sulforaphane increases the activity of phase I and phase II of the drug metabolizing enzymes .…”

“…Sulforaphane has been shown to exhibit anticancer activities via several mechanisms such as inhibition of DNA methylation, reactivation of nuclear factor E2‐related factor 2 (Nrf2), inhibition of p21 and silencing of tumor promoting genes . Sulforaphane increases the activity of phase I and phase II of the drug metabolizing enzymes . It binds to reactive thiol groups especially those in cysteines leading to defect in protein function .…”