Cordycepin suppresses TNF-α-induced NF-κB activation by reducing p65 transcriptional activity, inhibiting IκBα phosphorylation, and blocking IKKγ ubiquitination

Cordycepin is reported to participate in multiple pharmacological activities including anti-tumor and anti-inflammation, and is involved in the regulation of NF-kappa B signaling pathway. However, the detailed molecular mechanism of cordycepin in suppression of NF-kappa B signaling pathway remains ambiguous. In this study, we first analyzed the effect of cordycepin on NF-kappa B activity in HEK-293T cells, and found that cordycepin resulted in a dose-dependent reduction in TNF-alpha-induced NF-kappa B activation. Although cordycepin did not block TNF-alpha-induced nuclear translocation of p65, high concentration of cordycepin reduced the DNA-binding and transcriptional activities of NF-kappa B. Moreover, cordycepin also inhibited I kappa B alpha phosphorylation so as to suppress the degradation of I kappa B alpha. Further investigation revealed that cordycepin suppressed IKKs-mediated NF-kappa B activation and inhibited the ubiquitination of IKK-gamma. In conclusion, cordycepin effectively inhibits NF-kappa B signaling through suppressing the activities of NF-kappa B, I kappa B and IKK. Thus, cordycepin may provide some potential therapeutic application in inflammation-associated disorders and cancer. (C) 2012 Elsevier B.V. All rights reserved.