Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2.

ABSTRACT: Background:Ginsenoside compound K(C-K), a major metabolite of ginsenoside, exhibits anticancer activity in various cancer cells and animal models. A cell signaling study has shown that C-K inhibited nuclear factor-kappa B (NF-?B) pathway in human astroglial cells and liver cancer cells. However, the molecular targets of C-K and the initiating events were not elucidated. Methods:Interaction between C-K and Annexin A2 was determined by molecular docking and thermal shift assay. HepG2 cells were treated with C-K, followed by a luciferase reporter assay for NF-?B, immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-?B p50 subunit, coimmunoprecipitation of Annexin A2 and NF-?B p50 subunit, and both cell viability assay and plate clone formation assay to determine the cell viability. Results:Both molecular docking and thermal shift assay positively confirmed the interaction between Annexin A2 and C-K. This interaction prevented the interaction between Annexin A2 and NF-?B p50 subunit and their nuclear colocalization, which attenuated the activation of NF-?B and the expression of its downstream genes, followed by the activation of caspase 9 and 3. In addition, the overexpression of Annexin A2-K320A, a C-K binding-deficient mutant of Annexin A2, rendered cells to resist C-K treatment, indicating that C-K exerts its cytotoxic activity mainly by targeting Annexin A2. Conclusion:This study for the first time revealed a cellular target of C-K and the molecular mechanism for its anticancer activity.

SUBMITTER: Wang YS 

PROVIDER: S-EPMC6606818 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature