Resveratrol enhances solar UV-induced responses in normal human epidermal keratinocytes

Saveria Pastore, Daniela Lulli, Antonia Pascarella, Riccardo Maurelli, Elena Dellambra, Alla Potapovich, Vladimir Kostyuk, Chiara De Luca, Liudmila Korkina

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Resveratrol (RV) differentially affects UV-induced death/pro-survival pathways in normal and tumor cells. On these grounds, RV-containing topical products have been developed to prevent UV-associated tumorigenesis/damage to human skin. In this study, we evaluated mechanisms of combined effects of RV and low-dose solar simulated UVA+UVB or 6-formylindo[3,2-b]carbazole (FICZ), a product of tryptophan photo-oxidation known to mediate UV effects, on the inflammatory, metabolic and proliferative responses of cultured normal human epidermal keratinocytes (HEK). Applied alone, RV, UV and FICZ induced time- and dose-dependent activation of aryl hydrocarbon receptor (AhR) pathway followed by over-expression of Cyp1A1 (metabolic response), UV and RV induced IL-8 expression (inflammatory response), while RV enhanced also HEK proliferation revealed by MTT assay and 3H-thymidine incorporation. In the combined treatment, RV synergized with both UV and FICZ, leading to further activation of AhR machine, Cyp1A1 transcription and IL-8 expression, the latter partly AhR-dependent as assessed by AhR silencing. RV enhanced UV-induced NFkappaB activation and nuclear translocation of epidermal growth factor receptor. By contrast, proliferative effect of RV was abolished in the presence of UV, whereas synergic anti-proliferative action of RV+UV was observed in the Nrf2-silenced HEK. Our data suggest cooperative effects of RV-specific and UV-/FICZ-activated transcription factors leading to deregulated inflammatory, metabolic and proliferative responses of HEK.

Original languageEnglish
Pages (from-to)1522-1530
Number of pages9
JournalPhotochemistry and Photobiology
Issue number6
Publication statusPublished - Nov 2012

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Biochemistry
  • Medicine(all)


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