Many intracellular effects have been attributed to resveratrol, a polyphenolic phytoalexin found in grapes and in other plants, including the direct regulation of transcription. Here, we have analyzed the impact of resveratrol on gene transcription regulated by the cyclic AMP response element (CRE).Methods and results:
Transcription of a chromatin-embedded reporter gene with CREs in its regulatory region was significantly elevated in resveratrol-treated 293 human embryonic kidney cells, hepatoma cells and neural stem cells. The CRE thus functions as resveratrol-responsive element. The polyphenols quercetin and naringenin also stimulated CRE-mediated gene transcription, but not in the range of resveratrol. The polyphenol curcumin, in contrast, had no effect upon CRE-regulated transcription. In addition, resveratrol stimulation upregulated the transcriptional activation potentials of the CRE-binding proteins (CREB) and activating transcription factor 2 (ATF2).Conclusion:
CREB exhibits cytoprotective activity by stimulating CRE-regulated genes, while ATF2 has been identified as a tumor suppressor. The fact that resveratrol upregulates CRE-mediated gene transcription and enhances the transcriptional activation potentials of CREB and ATF2 suggests that cytoprotective and tumor suppressive activities of resveratrol may rely—at least in part—on the stimulation of CREB- and ATF2-controlled target genes.