Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression
Aurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. However, the effects of radot...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2019-05-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428319848612 |
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| author | Sook-Kyoung Heo Eui-Kyu Noh Yoo Kyung Jeong Lan Jeong Ju Jun Young Sung Ho-Min Yu Jaekyung Cheon SuJin Koh Young Joo Min Yunsuk Choi Jae-Cheol Jo |
| author_facet | Sook-Kyoung Heo Eui-Kyu Noh Yoo Kyung Jeong Lan Jeong Ju Jun Young Sung Ho-Min Yu Jaekyung Cheon SuJin Koh Young Joo Min Yunsuk Choi Jae-Cheol Jo |
| author_sort | Sook-Kyoung Heo |
| collection | DOAJ |
| description | Aurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. However, the effects of radotinib on Aurora kinase expression in acute myeloid leukemia are not well studied. Interestingly, the cytotoxicity of acute myeloid leukemia cells was increased by radotinib treatment. Radotinib significantly decreased the expression of cyclin-dependent kinase 1 and cyclin B1, the key regulators of G2/M phase, and inhibited the expression of Aurora kinase A and Aurora kinase B in acute myeloid leukemia cells. In addition, radotinib decreased the expression and binding between p-Aurora kinase A and TPX2, which are required for spindle assembly. Furthermore, it reduced Aurora kinase A and polo-like kinase 1 phosphorylation and suppressed the expression of α-, β-, and γ-tubulin in acute myeloid leukemia cells. Furthermore, radotinib significantly suppressed the key regulators of G2/M phase including cyclin B1 and Aurora kinase A in a xenograft animal model. Therefore, our results suggest that radotinib can abrogate acute myeloid leukemia cell growth both in vitro and in vivo and may serve as a candidate agent or a chemosensitizer for treating acute myeloid leukemia. |
| format | Article |
| id | doaj-art-8851fa8ef86e48d6b82ff7d75b2d0a5e |
| institution | Matheson Library |
| issn | 1423-0380 |
| language | English |
| publishDate | 2019-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-8851fa8ef86e48d6b82ff7d75b2d0a5e2025-08-02T13:02:42ZengSAGE PublishingTumor Biology1423-03802019-05-014110.1177/1010428319848612Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expressionSook-Kyoung Heo0Eui-Kyu Noh1Yoo Kyung Jeong2Lan Jeong Ju3Jun Young Sung4Ho-Min Yu5Jaekyung Cheon6SuJin Koh7Young Joo Min8Yunsuk Choi9Jae-Cheol Jo10Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaDepartment of Hematology and Oncology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaBiomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaBiomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaBiomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaBiomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaDepartment of Hematology and Oncology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaDepartment of Hematology and Oncology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaDepartment of Hematology and Oncology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaDepartment of Hematology and Oncology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaDepartment of Hematology and Oncology, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, Republic of KoreaAurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. However, the effects of radotinib on Aurora kinase expression in acute myeloid leukemia are not well studied. Interestingly, the cytotoxicity of acute myeloid leukemia cells was increased by radotinib treatment. Radotinib significantly decreased the expression of cyclin-dependent kinase 1 and cyclin B1, the key regulators of G2/M phase, and inhibited the expression of Aurora kinase A and Aurora kinase B in acute myeloid leukemia cells. In addition, radotinib decreased the expression and binding between p-Aurora kinase A and TPX2, which are required for spindle assembly. Furthermore, it reduced Aurora kinase A and polo-like kinase 1 phosphorylation and suppressed the expression of α-, β-, and γ-tubulin in acute myeloid leukemia cells. Furthermore, radotinib significantly suppressed the key regulators of G2/M phase including cyclin B1 and Aurora kinase A in a xenograft animal model. Therefore, our results suggest that radotinib can abrogate acute myeloid leukemia cell growth both in vitro and in vivo and may serve as a candidate agent or a chemosensitizer for treating acute myeloid leukemia.https://doi.org/10.1177/1010428319848612 |
| spellingShingle | Sook-Kyoung Heo Eui-Kyu Noh Yoo Kyung Jeong Lan Jeong Ju Jun Young Sung Ho-Min Yu Jaekyung Cheon SuJin Koh Young Joo Min Yunsuk Choi Jae-Cheol Jo Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression Tumor Biology |
| title | Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression |
| title_full | Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression |
| title_fullStr | Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression |
| title_full_unstemmed | Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression |
| title_short | Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression |
| title_sort | radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of aurora kinase a expression |
| url | https://doi.org/10.1177/1010428319848612 |
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