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KMID : 0352720190430030452
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Journal of Ginseng Research
2019 Volume.43 No. 3 p.452 ~ p.459
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Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2
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Wang Yu-Shi
Zhu Hongyan
Li He
Li Yang
Zhao Bing
Jin Ying-Hua
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Abstract
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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-κB) 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-кB, immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-кB p50 subunit, coimmunoprecipitation of Annexin A2 and NF-кB 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-кB p50 subunit and their nuclear colocalization, which attenuated the activation of NF-кB 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.
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KEYWORD
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Annexin A2, Compound K, Hepatocellular carcinoma, NF-кB
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