Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression
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 stud...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-05-01
|
| Series: | Journal of Ginseng Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1226845321001639 |
| _version_ | 1818270831182086144 |
|---|---|
| author | Jihee Hong Dasom Gwon Chang-Young Jang |
| author_facet | Jihee Hong Dasom Gwon Chang-Young Jang |
| author_sort | Jihee Hong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T21:16:31Z |
| format | Article |
| id | doaj.art-143ff89ca4ee4987954f866e735d357c |
| institution | Directory Open Access Journal |
| issn | 1226-8453 |
| language | English |
| last_indexed | 2024-12-12T21:16:31Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Ginseng Research |
| spelling | doaj.art-143ff89ca4ee4987954f866e735d357c2022-12-22T00:11:44ZengElsevierJournal of Ginseng Research1226-84532022-05-01463481488Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progressionJihee Hong0Dasom Gwon1Chang-Young Jang2Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of KoreaResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of KoreaCorresponding author. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.; Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of KoreaBackground: 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.http://www.sciencedirect.com/science/article/pii/S1226845321001639Aurora BCancerGinsenoside Rg1Haspin kinaseMitosis |
| spellingShingle | Jihee Hong Dasom Gwon Chang-Young Jang Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression Journal of Ginseng Research Aurora B Cancer Ginsenoside Rg1 Haspin kinase Mitosis |
| title | Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression |
| title_full | Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression |
| title_fullStr | Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression |
| title_full_unstemmed | Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression |
| title_short | Ginsenoside Rg1 suppresses cancer cell proliferation through perturbing mitotic progression |
| title_sort | ginsenoside rg1 suppresses cancer cell proliferation through perturbing mitotic progression |
| topic | Aurora B Cancer Ginsenoside Rg1 Haspin kinase Mitosis |
| url | http://www.sciencedirect.com/science/article/pii/S1226845321001639 |
| work_keys_str_mv | AT jiheehong ginsenosiderg1suppressescancercellproliferationthroughperturbingmitoticprogression AT dasomgwon ginsenosiderg1suppressescancercellproliferationthroughperturbingmitoticprogression AT changyoungjang ginsenosiderg1suppressescancercellproliferationthroughperturbingmitoticprogression |