[Show abstract][Hide abstract] ABSTRACT: Dietary phenolics may play a protective role in UV-mediated skin pigmentation through their antioxidant and UV-absorbing actions. In this study, we investigated whether genetic silencing of Nrf2, regulating the transcription of antioxidant genes, affected melanogenesis in primary human epidermal melanocytes (HEMn) and B16F10 melanoma cells subjected to UVA (8J/cm2) exposure. Then, we explored the antimelanogenic actions of phenolics; caffeic acid (CA) and ferulic acid (FA) providing partial UVA protection; quercetin (QU) and rutin (RU) providing strong UVA protection and; avobenzone (AV), an efficient UVA filter, in association with modulation of Nrf2-mediated antioxidant defenses in response to UVA insults in B16F10 cells. Upon oxidative insults, Nrf2 silencing promoted melanogenesis in both HEMn and B16F10 cells irradiated with UVA. Stimulation of melanogenesis by UVA correlated with increased ROS and oxidative DNA damage (8-OHdG), GSH depletion as well as a transient downregulation of Nrf2 nuclear translocation and of Nrf2-ARE signaling in B16F10 cells. All test compounds exerted antimelanogenic effects with respect to their abilities to reverse UVA-mediated oxidative damage as well as downregulation of Nrf2 activity and its target antioxidants (GCLC, GST and NQO1) in B16F10 cells. In conclusion, defective Nrf2 may promote melanogenesis under UVA irradiation through oxidative stress mechanisms. Compounds with antioxidant and/or UVA absorption properties could protect against UVA-induced melanogenesis through indirect regulatory effect on Nrf2-ARE pathway.
[Show abstract][Hide abstract] ABSTRACT: Oxidative stress has been suggested to play a role in ultraviolet A (UVA)-mediated melanogenesis. Glutathione (GSH) and GSH-related enzymes including γ-glutamate cysteine ligase (γ-GCL) and glutathione S-transferase (GST) are important antioxidant defenses responsible for maintaining cellular redox balance. Hence, improving GSH redox system to cope with oxidative insults may be essential for attenuation of abnormal melanin production. Gallic acid (GA), a dietary phenolic, has been shown to provide beneficial effects against hyperpigmentation possibly through its antioxidant properties. This study thus aimed to assess the antimelanogenic action of GA with regard to modulation of GSH-GCL system and GST in two melanoma cell lines, lightly pigmented G361 human melanoma and more pigmented B16F10 mouse melanoma cells, irradiated with UVA. G361 cells were shown to have lower basal GSH content and GST activity than B16F10 cells. Moreover, GA provided antimelanogenic effects in correlation with promotion of GSH levels, GST activity as well as γ-GCL and GST mRNA in both G361 and B16F10 cells at 2-h post-irradiation. In summary, GA exhibits protective effects on UVA-mediated melanogenesis possibly through improvement of GSH-related antioxidant defenses. Furthermore, different redox state in G361 and B16F10 cells may affect the responses of melanoma cells to GA.
Full-text · Article · Mar 2012 · Journal of photochemistry and photobiology. B, Biology