Curcumin derivative C817 inhibits proliferation of imatinib-resistant chronic myeloid leukemia cells with wild-type or mutant Bcr-Abl in vitro
文献类型：期刊论文
| 作者 | Wu, Li-xian2,3,4; Wu, Ying3,4; Chen, Rui-jia2,3; Liu, Yang3,4,5; Huang, Li-sen2,3; Lou, Li-guang1 ; Zheng, Zhi-hong6; Chen, Yuan-zhong6; Xu, Jian-hua2,3,4
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2014-03 |
| 卷号 | 35期号:3页码:401-409 |
| 关键词 | chronic myelogenous leukemia imatinib resistance Bcr-Abl mutantion curcumin C817 leukemia stem cell |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2013.180 |
| 文献子类 | Article |
| 英文摘要 | Aim: To find new kinase inhibitors that overcome the imatinib resistance in treatment of chronic myeloid leukemia (CML), we synthesized C817, a novel derivative of curcumin, and tested its activities against wild-type (WT) and imatinib-resistant mutant Abl kinases, as well as in imatinib-sensitive and resistant CML cells in vitro. Methods: 32D cells harboring WT or mutant Abl kinases (nucleotide binding P-loop mutants Q252H, Y253F, and imatinib contact residue mutant T315I), as well as K562/G01 cells (with whole Bcr-Abl gene amplication) were tested. Kinase activity was measured using Kinase-Glo Luminescent Kinase Assay Platform in recombinant WT and mutant (Q252H, Y253F, and T315I) Abl kinases. Cell proliferation and apoptosis were examined using MTT assay and flow cytometry, respectively. The phosphorylation levels of Bcr-Abl initiated signaling proteins were analyzed using Western blotting. Colony forming units (CFU) growth and long term culture-initiating cells (LTC-ICs) were used to test the effects of C817 on human leukemia progenitor/stem cells. Results: C817 potently inhibited both WT and mutant (Q252H, Y253F, and T315I) Abl kinase activities in a non-ATP competitive manner with the values of IC50 at low nanomole levels. In consistent with above results, C817 suppressed the growth of both imatinib-sensitive and resistant CML cells, including wild-type K562, K562/G01, 32D-T315I, 32D-Q252H, and 32D-Y253F cells with the values of IC50 at low micromole levels. C817 (0.5 or 1 mu mol/L) dose-dependently inhibited the phosphorylation of Bcr-Abl and downstream proteins STAT-5 and CrkL in imatinib-resistant K562/G01 cells. Furthermore, C817 significantly suppressed CFU growth and LTC-ICs, implicating that C817 could eradiate human leukemia progenitor/stem cells. Conclusion: C817 is a promising compound for treatment of CML patients with Bcr-Abl kinase domain mutations that confer imatinib resistance. |
| WOS关键词 | MITOCHONDRIAL PATHWAY ; SELECTIVE INHIBITOR ; CLINICAL RESISTANCE ; BINDING-SITE ; STEM-CELLS ; APOPTOSIS ; KINASE ; ATP ; NILOTINIB ; DISORDER |
| 资助项目 | National Natural Science Foundation of China[30901824] ; National Natural Science Foundation of China[81173096] ; National Natural Science Foundation of China[81273541] ; National Natural Science Foundation of China[30873101] ; National Natural Science Foundation of China[30472187] ; National Science and Technology Foundation of China for Key Projects of "Major New Drugs Innovation and Development"[2012ZX09103-101-028] ; Natural Science Foundation of Fujian Province of China (Outstanding Project)[2011J06013] ; Educational Bureau of Fujian Province of China[JA11101] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000332467200011 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277172]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wu, Li-xian |
| 作者单位 | 1.Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Fujian Med Univ, Sch Pharm, Dept Pharmacol, Fuzhou 350004, Peoples R China; 3.Fujian Med Univ, Sch Pharm, Inst Mat Med, Fuzhou 350004, Peoples R China; 4.Fujian Med Univ, Sch Pharm, Fuijan Key Lab Nat Med Pharmacol, Fuzhou 350004, Peoples R China; 5.Fujian Med Univ, Sch Pharm, Dept Pharmacochem, Fuzhou 350004, Peoples R China; 6.Fujian Med Univ, Union Hosp, Fujian Inst Hematol, Fuzhou 350001, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wu, Li-xian,Wu, Ying,Chen, Rui-jia,et al. Curcumin derivative C817 inhibits proliferation of imatinib-resistant chronic myeloid leukemia cells with wild-type or mutant Bcr-Abl in vitro[J]. ACTA PHARMACOLOGICA SINICA,2014,35(3):401-409. |
| APA | Wu, Li-xian.,Wu, Ying.,Chen, Rui-jia.,Liu, Yang.,Huang, Li-sen.,...&Xu, Jian-hua.(2014).Curcumin derivative C817 inhibits proliferation of imatinib-resistant chronic myeloid leukemia cells with wild-type or mutant Bcr-Abl in vitro.ACTA PHARMACOLOGICA SINICA,35(3),401-409. |
| MLA | Wu, Li-xian,et al."Curcumin derivative C817 inhibits proliferation of imatinib-resistant chronic myeloid leukemia cells with wild-type or mutant Bcr-Abl in vitro".ACTA PHARMACOLOGICA SINICA 35.3(2014):401-409. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。