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).
CONCLUSIONS: 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.