Unknown

Dataset Information

0

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


ABSTRACT: 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.

SUBMITTER: Wang YS 

PROVIDER: S-EPMC5966357 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC3906106 | biostudies-literature
| S-EPMC8510405 | biostudies-literature
| S-EPMC6496896 | biostudies-literature
| S-EPMC8829491 | biostudies-literature
| S-EPMC6529991 | biostudies-literature
| S-EPMC6921372 | biostudies-literature
| S-EPMC2836041 | biostudies-literature
2021-01-14 | GSE164801 | GEO
| S-EPMC4690797 | biostudies-literature
| S-EPMC4694965 | biostudies-literature