Induction of Quinone Reductase NQO1 by Resveratrol Involves Antioxidant Response Element ARE and is Accompanied by Nuclear Translocation of Transcription Factor Nrf2

The phytochemical resveratrol has been reported to induce NQO1, an enzyme involved in detoxification reactions, by as yet undetermined mechanisms. Using K562 cells as a model, we showed that 25-50 μM resveratrol caused an optimal increase in NQO1 that peaked at 48 h. A 2.5-fold induction in NQO1 protein expression was accompanied by a 1.8-fold elevation in mRNA levels and a greater than 5-fold increase in NQO1 enzymatic activity. Real-time PCR analysis showed that resveratrol caused a maximum increase in NQO1 mRNA copy number at 24 h. Using fluorescent microscopy in combination with transfection experiments with plasmids harboring different promoter elements of NQO1 linked to a luciferase reporter gene, we demonstrated that modulation of NQO1 gene expression by resveratrol involved the ARE, concomitant with or accompanied by a change in the cellular localization of the transcription factor Nrf2. The results indicate that resveratrol disrupts the Nrf2-Keap1 complex and facilitates the translocation of Nrf2 into the nucleus where it locates ARE, leading to activation of transcription of NQO1.