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Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression

Authors
Hong, J.Gwon, D.Jang, C.-Y.
Issue Date
May-2022
Publisher
Elsevier B.V.
Keywords
Aurora B; Cancer; Ginsenoside Rg1; Haspin kinase; Mitosis
Citation
Journal of Ginseng Research, v.46, no.3, pp.481 - 488
Journal Title
Journal of Ginseng Research
Volume
46
Number
3
Start Page
481
End Page
488
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/151370
DOI
10.1016/j.jgr.2021.11.004
ISSN
1226-8453
Abstract
Background: Although the tumor-suppressive effects of ginsenosides in cell cycle have been well established, their pharmacological properties in mitosis have not been clarified yet. The chromosomal instability resulting from dysregulated mitotic processes is usually increased in cancer. In this study, we aimed to investigate the anticancer effects of ginsenoside Rg1 on mitotic progression in cancer. Materials and methods: Cancer cells were treated with ginsenoside Rg1 and their morphology and intensity of different protein were analyzed using immunofluorescence microscopy. The level of proteins in chromosomes was compared through chromosomal fractionation and Western blot analyses. The location and intensity of proteins in the chromosome were confirmed through immunostaining of mitotic chromosome after spreading. The colony formation assays were conducted using various cancer cell lines. Results: Ginsenoside Rg1 reduced cancer cell proliferation in some cancers through inducing mitotic arrest. Mechanistically, it inhibits the phosphorylation of histone H3 Thr3 (H3T3ph) mediated by Haspin kinase and concomitant recruitment of chromosomal passenger complex (CPC) to the centromere. Depletion of Aurora B at the centromere led to abnormal centromere integrity and spindle dynamics, thereby causing mitotic defects, such as increase in the width of the metaphase plate and spindle instability, resulting in delayed mitotic progression and cancer cell proliferation. Conclusion: Ginsenoside Rg1 reduces the level of Aurora B at the centromere via perturbing Haspin kinase activity and concurrent H3T3ph. Therefore, ginsenoside Rg1 suppresses cancer cell proliferation through impeding mitotic processes, such as chromosome alignment and spindle dynamics, upon depletion of Aurora B from the centromere. © 2021
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