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Pharmacol Ther. 2018 Oct;190:187-201. doi: 10.1016/j.pharmthera.2018.06.001. Epub 2018 Jun 8.

From chemo-prevention to epigenetic regulation: The role of isothiocyanates in skin cancer prevention.

Author information

1
Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, UK.
2
The Watercress Company/The Wasabi Company, Dorset, UK.
3
Redox Biology Centre and School of Veterinary Medicine & Biomedical Sciences, University of Nebraska, Lincoln, USA; School of Veterinary Medicine & Biomedical Sciences, University of Nebraska, Lincoln, USA.
4
National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry & Biotechnology, Athens, Greece.
5
Department of Molecular Biology & Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
6
Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, UK. Electronic address: m.panagiotidis@northumbria.ac.uk.

Abstract

Skin cancer incidence is rapidly growing over the last decades and is generally divided into malignant melanoma and non-melanoma (NMSC) with the latter being subdivided into squamous (SCC) and basal cell carcinoma (BCC). Among them, melanoma is the most aggressive type with high mortality rates. On the other hand, aberrant gene expression is a critical step towards malignant transformation. To this end, epigenetic modifications like changes in DNA methylation patterns and miRNA expression profile as well as histone modifications are all capable of inducing an altered gene expression profile involved in various cellular cascades including cell cycle, proliferation and apoptosis. In general, there is an interest about the beneficiary effect of various phytochemicals in the prevention and treatment of skin malignancies. Among them, glucosinolates are an important type of compounds, abundant in cruciferous vegetables, which are hydrolysed by an endogenous enzyme called myrosinase to a range of bioactive compounds including isothiocyanates (ITCs). These are the major biologically active products capable of mediating the anti-cancer effect of cruciferous vegetables. Their chemo-preventive action is mainly attributed to a plurality of anti-cancer properties including regulation of the epigenetic machinery. Current evidence supports the view that ITCs are potent compounds in interacting with the epigenome in order to restore the normal epigenetic landscape in malignant cells. This review article summarizes the current state of knowledge on the epigenetic modifications that lead to malignant transformation and the role of ITCs with respect to their ability to restore the epigenetic landscape that contributes to skin carcinogenesis.

KEYWORDS:

Basal cell carcinoma; Chemoprevention; Epigenetic regulation; Isothiocyanates; Melanoma; Non-melanoma skin cancer; Skin cancer; Squamous cell carcinoma; Sulforaphane

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