Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: Role of Nrf2-dependent gene expression and antioxidant enzymes

Chronic UVR-exposure may impair the stress response and antioxidant defense mechanisms of human skin. The transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2) orchestrates the expression of genes coding for the stress response and antioxidant proteins. Here, we tested sulforaphane (SFN) and phenylethyl isothiocyanate (PEITC) for their ability to counteract UVR-induced oxidative stress and apoptosis in ex vivo human full-thickness skin combined with in vitro HaCaT keratinocytes. Investigation of Nrf2 transactivation and induction of genes coding for Nrf2-dependent phase II antioxidative enzymes (γ-glutamylcysteine-synthetase (γGCS), heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1)) was performed in HaCaT keratinocytes. Comparative investigations in human ex vivo skin were conducted for analysis of gene expression of above mentioned phase II enzymes and catalase (CAT) as well as hematoxylin/eosin (H&E) and immunofluorescence (catalase, cleaved Casp-3). UVR exposure of human skin (300mJ/cm2) resulted in a significant time-dependent increase of the number of sunburn cells and caspase-3 activation as biomarkers of apoptosis for up to 48h (p