title: Resveratrol inhibits NF-kB signaling through suppression of p65 and IkappaB kinase activities.
abstract: Resveratrol has been shown to possess multiple pharmacological activities including anti-tumor, anti-inflammation and immunomodulation, and participates in the regulation of the NF-kappaB signaling pathway. However, the mechanism of the NF-kappaB signaling pathway inhibited by resveratrol remains obscure. In this study, we first examined the effect of resveratrol on endogenous and TNF-alpha-induced NF-kappaB activation, and found that resveratrol suppressed NF-kappaB activation in a dose dependent manner. Resveratrol reduced the transcriptional activity of p65, but neither affected the DNA-binding activity of NF-kappaB nor blocked the nuclear translocation of p65. Moreover, resveratrol had no effect on the expression level of IkappaBalpha protein and inhibited IkappaBalpha degradation. Further investigation revealed that resveratrol blocked the ubiquitination of NEMO and inhibited IkappaB kinase(beta)-mediated NF-kappaB activation. These results demonstrated that resveratrol effectively suppressed NF-kappaB signaling through inhibiting the activities of NF-kappaB and IkappaB kinase. Therefore, resveratrol may provide a novel approach to treating inflammation-associated diseases and cancer.
authors.affiliation: Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou, China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Ren
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cui
authors.forename: Zeren
authors.initials: Z
authors.lastname: Huoc
authors.forename: Jinru
authors.initials: J
authors.lastname: Xue
authors.forename: Hao
authors.initials: H
authors.lastname: Cui
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Mao
authors.forename: Rirong
authors.initials: R
authors.lastname: Yang
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D047468:Immunoprecipitation; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010957:Plasmids / Q000235:genetics; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors*; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D013267:Stilbenes; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases; D051550:I-kappa B Kinase; D000077185:Resveratrol