Phytochemicals as Protectors Against Ultraviolet Radiation: Versatility of Effects and Mechanisms

Abstract

Ultraviolet (UV) radiation is one of the most abundant carcinogens in our environment, and the development of non-melanoma skin cancers, the most common type of human malignancy worldwide, represents one of the major consequences of excessive exposure. Because of growing concerns that the level of UV radiation is increasing as a result of depletion of the stratospheric ozone and climate change, the development of strategies for protection of the skin is an urgent need. Many phytochemicals that belong to various families of secondary metabolites, such as alkaloids (caffeine, sanguinarine), flavonoids [(−)-epigallocatechin 3-gallate, genistein, silibinin], carotenoids ( β -carotene, lycopene), and isothiocyanates (sulforaphane), offer exciting platforms for the development of such protective strategies. These phytochemicals have been consumed by humans for many centuries as part of plant-rich diets and are presumed to be of low toxicity, an essential requirement for a chemoprotective agent. Mechanistically, they affect multiple signalling pathways and protect against UV radiation-inflicted damage by their ability to act as direct and indirect antioxidants, as well as anti-inflammatory and immunomodulatory agents. Such ”pluripotent character” is a critical prerequisite for an agent that is designed to counteract the multiple damaging effects of UV radiation. Especially attractive are inducers of the Keap1/Nrf2/ARE pathway, which controls the gene expression of proteins whose activation leads to enhanced protection against oxidants and electrophiles. Such protection is comprehensive, long-lasting, and unlikely to cause pro-oxidant effects or interfere with the synthesis of vitamin D. Abbreviations AP-1:activator protein 1 ARE:antioxidant response element COX-2:cyclooxygenase 2 EGG:epigallocatechin 3-gallate EGF:epidermal growth factor GSH:glutathione iNOS:inducible nitric oxide synthase Keap1:Kelch-like ECH-associated protein 1 IL:inerleukin MAPK:mitogen-activated protein kinase MMP:matrix metalloprotease NF-κB:nuclear factor-κB NQO1:NAD(P)H:quinone oxidoreductase 1 Nrf2:nuclear factor-erythroid 2-related factor 2 ODC:ornithine decarobxylase PCNA:proliferating cell nuclear antigen ROS:reactive oxygen species TPA:12- O -tetradecanoylphorbol 13-acetate UV:ultraviolet