Volume 9 Issue 6
Jun.  2018
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Yu-Shi Wang, He Li, Yang Li, Hongyan Zhu, Ying-Hua Jin. Identification of natural compounds targeting Annexin A2 with an anti-cancer effect[J]. Protein&Cell, 2018, 9(6): 568-579. doi: 10.1007/s13238-018-0513-z
Citation: Yu-Shi Wang, He Li, Yang Li, Hongyan Zhu, Ying-Hua Jin. Identification of natural compounds targeting Annexin A2 with an anti-cancer effect[J]. Protein&Cell, 2018, 9(6): 568-579. doi: 10.1007/s13238-018-0513-z

Identification of natural compounds targeting Annexin A2 with an anti-cancer effect

doi: 10.1007/s13238-018-0513-z
Funds:

This study was funded by Provincial Project for Industrial Innovation Special Fund of Jilin Province (2017) and Special Project for Province and University Construction Plan of Jilin Province (SXGJXX2017-13).

  • Received Date: 2017-11-07
  • Rev Recd Date: 2018-01-24
  • Annexin A2, a multifunctional tumor associated protein, promotes nuclear factor-kappa B (NF-κB) activation by interacting with NF-κB p50 subunit and facilitating its nuclear translocation. Here we demonstrated that two ginsenosides Rg5 (G-Rg5) and Rk1 (G-Rk1), with similar structure, directly bound to Annexin A2 by molecular docking and cellular thermal shift assay. Both Rg5 and Rk1 inhibited the interaction between Annexin A2 and NF-κB p50 subunit, their translocation to nuclear and NF-κB activation. Inhibition of NF-κB by these two ginsenosides decreased the expression of inhibitor of apoptosis proteins (IAPs), leading to caspase activation and apoptosis. Over expression of K302A Annexin A2, a mutant version of Annexin A2, which fails to interact with G-Rg5 and G-Rk1, effectively reduced the NF-κB inhibitory effect and apoptosis induced by G-Rg5 and G-Rk1. In addition, the knockdown of Annexin A2 largely enhanced NF-κB activation and apoptosis induced by the two molecules, indicating that the effects of G-Rg5 and G-Rk1 on NF-κB were mainly mediated by Annexin A2. Taken together, this study for the first time demonstrated that G-Rg5 and G-Rk1 inhibit tumor cell growth by targeting Annexin A2 and NF-κB pathway, and G-Rg5 and G-Rk1 might be promising natural compounds for targeted cancer therapy.
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