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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.6
- 수록면
- 452 - 459 (8page)
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초록· 키워드
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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-kB) 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-kB, immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-kB p50 subunit, coimmunoprecipitation of Annexin A2 and NF-kB 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-kB p50 subunit and their nuclear colocalization, which attenuated the activation of NF-kB 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.
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-kB, immunofluorescence imaging for the subcellular localization of Annexin A2 and NF-kB p50 subunit, coimmunoprecipitation of Annexin A2 and NF-kB 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-kB p50 subunit and their nuclear colocalization, which attenuated the activation of NF-kB 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.
목차
ABSTRACT
1. Introduction
2. Materials and method
3. Results
4. Discussion
References
참고문헌 (34)
참고문헌 신청
Chun-Ying Liu / 2015 / Preparation of minor ginsenosides C-Mc, C-Y, F2, and C-K from American ginseng PPD-ginsenoside using special ginsenosidase type-I from Aspergillus niger g.848 / Journal of Ginseng Research 39(3):221~229
Taddesse Yayeh / 2016 / Morphine dependence is attenuated by red ginseng extract and ginsenosides Rh2, Rg3, and compound K / Journal of Ginseng Research 40(4):445~452
Jitendra Upadhyaya / 2016 / Enzymatic formation of compound-K from ginsenoside Rb1 by enzyme preparation from cultured mycelia of Armillaria mellea / Journal of Ginseng Research 40(2):105~112
Lei C / 2016 / Ginsenoside compound K sensitizes human colon cancer cells to TRAILinduced apoptosis via autophagy-dependent and -independent DR5 upregulation / Cell Death Dis 7(8):e2334
Sunghee C / 2009 / A metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells / BMC Cancer 9(1):449
Taddesse Yayeh / 2016 / Morphine dependence is attenuated by red ginseng extract and ginsenosides Rh2, Rg3, and compound K / Journal of Ginseng Research 40(4):445~452
Jitendra Upadhyaya / 2016 / Enzymatic formation of compound-K from ginsenoside Rb1 by enzyme preparation from cultured mycelia of Armillaria mellea / Journal of Ginseng Research 40(2):105~112
Lei C / 2016 / Ginsenoside compound K sensitizes human colon cancer cells to TRAILinduced apoptosis via autophagy-dependent and -independent DR5 upregulation / Cell Death Dis 7(8):e2334
Sunghee C / 2009 / A metabolite of ginseng saponin, induces apoptosis via caspase-8-dependent pathway in HL-60 human leukemia cells / BMC Cancer 9(1):449
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