https://scholars.lib.ntu.edu.tw/handle/123456789/564871
標題: | Induction of mitotic arrest and apoptosis by evodiamine in human leukemic T-lymphocytes | 作者: | Huang Y.-C. JIH-HWA GUH Teng C.-M. |
公開日期: | 2004 | 卷: | 75 | 期: | 1 | 起(迄)頁: | 35-49 | 來源出版物: | Life Sciences | 摘要: | Leukemias are a heterogenous group of diseases characterized by uncontrolled proliferation of abnormal blood cells of hematopoietic system. Evodiamine, a characteristic alkaloid extracted from Evodia fruits, has been reported to exhibit inhibitory effect on cell proliferation and migration in several types of cancer cells. However, there is no report elucidating the action target and anti-cancer mechanism of this potential natural compound. In this study, we have defined the anti-proliferative and apoptotic mechanisms of evodiamine in human acute leukemia CCRF-CEM cells. According to the MTT assay, the cell viability was inhibited by evodiamine in a concentration-dependent manner with an IC50 of 0.57 ± 0.05 μM. Flow cytometry analysis showed that the apoptotic cell death proceeded by evodiamine was accompanied with a cell cycle arrest at the G2/M phase. Using Wright-Giemsa staining, we observed that evodiamine caused the cells to arrest in mitosis. It also profoundly caused an increase in polymerized tubulin levels and Bcl-2 phosphorylation on serine 70 in these cells. These data imply that the microtubular cytoskeleton appears to be one of the cellular targets in response to evodiamine. Moreover, treatment of CCRF-CEM cells with evodiamine was associated with increased levels of pro-apoptotic protein Bax, activation of caspase-3, and proteolytic cleavage of poly (ADP-ribose) polymerase, an endogenous caspase-3 substrate. Taken together, we demonstrate that evodiamine causes the mitotic arrest and a consequent apoptosis in CCRF-CEM cells through the enhancement of polymerized tubulin levels. Furthermore, several biological events including the Bcl-2 phosphorylation, Bax up-regulation and increase of caspase-3 activity could explain evodiamine-induced cell apoptosis. ? 2004 Elsevier Inc. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-10344263866&doi=10.1016%2fj.lfs.2003.11.025&partnerID=40&md5=2d6157e949aef5f4be047a165cfb08b2 https://scholars.lib.ntu.edu.tw/handle/123456789/564871 |
ISSN: | 243205 | DOI: | 10.1016/j.lfs.2003.11.025 | SDG/關鍵字: | caspase 3; evodiamine; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein Bax; protein bcl 2; serine; tubulin; apoptosis; article; cell cycle G2 phase; cell viability; concentration response; controlled study; cytoskeleton; enzyme activation; enzyme substrate; flow cytometry; human; human cell; IC 50; leukemia cell; microtubule assembly; mitosis inhibition; protein degradation; protein phosphorylation; staining; T lymphocyte; Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Caspase 3; Caspases; Cell Survival; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Leukemia, T-Cell, Acute; Mitosis; Phosphorylation; Plant Extracts; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Quinazolines; T-Lymphocytes; Tubulin; Tumor Cells, Cultured; Evodia |
顯示於: | 藥學系 |
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