title: Cordycepin suppresses TNF-α-induced NF-κB activation by reducing p65 transcriptional activity, inhibiting IκBα phosphorylation, and blocking IKKγ ubiquitination.
abstract: Cordycepin is reported to participate in multiple pharmacological activities including anti-tumor and anti-inflammation, and is involved in the regulation of NF-κB signaling pathway. However, the detailed molecular mechanism of cordycepin in suppression of NF-κB signaling pathway remains ambiguous. In this study, we first analyzed the effect of cordycepin on NF-κB activity in HEK-293T cells, and found that cordycepin resulted in a dose-dependent reduction in TNF-α-induced NF-κB activation. Although cordycepin did not block TNF-α-induced nuclear translocation of p65, high concentration of cordycepin reduced the DNA-binding and transcriptional activities of NF-κB. Moreover, cordycepin also inhibited IκBα phosphorylation so as to suppress the degradation of IκBα. Further investigation revealed that cordycepin suppressed IKKs-mediated NF-κB activation and inhibited the ubiquitination of IKKγ. In conclusion, cordycepin effectively inhibits NF-κB signaling through suppressing the activities of NF-κB, IκB and IKK. Thus, cordycepin may provide some potential therapeutic application in inflammation-associated disorders and cancer.
authors.affiliation: Department of Biochemistry, College of Life Sciences, Sun Yat-Sen Zhongshan University, 135 Xingangxi Road, Guangzhou 510275, People's Republic of China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Ren
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cui
authors.forename: Zeren
authors.initials: Z
authors.lastname: Huo
authors.forename: Jinru
authors.initials: J
authors.lastname: Xue
authors.forename: Hao
authors.initials: H
authors.lastname: Cui
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.forename: Lanjin
authors.initials: L
authors.lastname: Jiang
authors.forename: Rirong
authors.initials: R
authors.lastname: Yang
mesh_terms: D003839:Deoxyadenosines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D054875:Ubiquitination; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D003839:Deoxyadenosines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D019892:eIF-2 Kinase; D051550:I-kappa B Kinase; C058120:cordycepin