In Vitro Characterization of Derrone as an Aurora Kinase Inhibitor
| Autor: | Yen Thi Hai Tran, Anh Thi Ngoc Nguyen, Nhung Thi My Hoang, Khanh Thi Van Bui, Thanh Lai Nguyen, Thuong Thien Phuong, Trang Thi Nhu Nguyen |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pharmacology Chemistry Kinase Aurora inhibitor Aurora B kinase Pharmaceutical Science macromolecular substances General Medicine Mitotic spindle checkpoint Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Aurora kinase 030220 oncology & carcinogenesis embryonic structures Endoreduplication Aurora Kinase B Aurora Kinase A biological phenomena cell phenomena and immunity |
| Zdroj: | Biological & Pharmaceutical Bulletin. 39:935-945 |
| ISSN: | 1347-5215 0918-6158 |
| DOI: | 10.1248/bpb.b15-00835 |
| Popis: | Among mitotic kinases, Aurora kinases are the most widely studied, since their expression is restricted to mitosis. They play a key role in chromosome segregation and cell polyploidy. Aurora kinases are important therapeutic targets, and several research groups have directed their efforts toward the identification of kinase inhibitors. The aim of this study is to screen and characterize Aurora kinase inhibitors from natural substances extracted from plants that are used in the Vietnamese pharmacopoeia. We have characterized in vitro Derrone, extracted from Erythrina orientalis L. MURR, as a novel Aurora kinase inhibitor. This compound exhibited an ability to inhibit the phosphorylation of histone H3 at ser10 both in kinase assay and at the cellular level. The compound was more effective against Aurora kinase B, with a lower IC50 value as compared to Aurora A. Moreover, it impaired the mitotic spindle checkpoint and led to endoreduplication in cancer cells, a phenomenon caused by an Aurora B inhibitor. Interestingly, using the xCelligence system and real-time cell analysis (RTCA) software, we set up a comparison of cell proliferation profiles between cancer cells treated with Derrone and VX680-a well-known Aurora kinase inhibitor-and we found that these profiles exhibited considerable similarity in cell morphology, growth, and death. Additionally, Derrone significantly inhibited the formation and growth of MCF7 tumor spheroids. |
| Databáze: | OpenAIRE |
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