Natural cyclopeptide RA-V inhibits the NF-κB signaling pathway by targeting TAK1.

Abstract

Rubiaceae-type cyclopeptides (RAs) are a type of plant cyclopeptides from the Rubia that have garnered significant attention owing to their unique bicyclic structures and amazing antitumour activities. Our recent work has shown that RAs suppress inflammation and angiogenesis and induce apoptosis. However, the underlying mechanism and targets remained unknown. Nuclear factor κB (NF-κB) signaling pathway plays a critical role in these biological processes, prompting us to investigate whether and how RAs affect this pathway. By screening compound libraries using NF-κB-dependent luciferase reporter, we observed that RA-V is the best NF-κB inhibitor. Further experiments demonstrated that RA-V interrupted the TAK1-TAB2 interaction and targeted TAK1 in this pathway. Moreover, RA-V prevented endotoxin shock and inhibited NF-κB activation and tumor growth in vivo. These findings clarify the mechanism of RA-V on NF-κB pathway and might account for the majority of known bioactivities of RA-V, which will help RA-V develop as new antiinflammatory and antitumour therapies.

• Authors: Zhe Wang, Simeng Zhao, Lihua Song, Yuzhi Pu, Qiang Wang, Guangzhi Zeng, Xing Liu, Ming Bai, Shao Li, Fabao Gao, Lijuan Chen, Chen Wang, Ninghua Tan
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 7 Pg. 715 (06 18 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 29915207 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biological Products
• NF-kappa B
• Peptides, Cyclic
• RA V
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7

Topics

• Animals
• Biological Products (pharmacology)
• Down-Regulation (drug effects)
• HEK293 Cells
• HeLa Cells
• Humans
• MAP Kinase Kinase Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Mice
• NF-kappa B (metabolism)
• Peptides, Cyclic (pharmacology)
• Protein Binding
• Signal Transduction (drug effects)