Nanomolar concentration of nsc606985, a camptothecin analog, induces leukernic-cell apoptosis through protein kinase c delta-dependent mechanisms
文献类型：期刊论文
| 作者 | Song, MG; Gao, SM; Du, KM; Xu, M; Yu, Y; Zhou, YH; Wang, Q; Chen, Z; Zhu, YS; Chen, GQ |
| 刊名 | Blood
 |
| 出版日期 | 2005-05-01 |
| 卷号 | 105期号:9页码:3714-3721 |
| ISSN号 | 0006-4971 |
| DOI | 10.1182/blood-2004-10-4011 |
| 通讯作者 | Chen, gq() |
| 英文摘要 | As a promising new class of anticancer drugs, camptothecins have advanced to the forefront of several areas of therapeutic and developmental chemotherapy. in the present study, we report that nsc606985, a rarely studied camptothecin analog, induces apoptosis in acute myeloid leukemia (aml) cells nb4 and u937 and inhibits the proliferation without cell death in breakpoint cluster region-abelson murine leukemia (bcr-abl) kinase-carrying leukemic k562 cells. for apoptosis induction or growth arrest, nanomolar concentrations of nsc606985 are sufficient. at such low concentrations, this agent also significantly inhibits the clonogenic activity of hematopoietic progenitors from patients with aml. for apoptosis induction, nsc606985 rapidly induces the proteolytic activation of protein kinase c delta (pkc delta) with loss of mitochondrial transmembrane. potential (delta psi m) and caspase-3 activation. cotreatment with rottlerin, a pkc delta-specific inhibitor, completely blocks nsc606985-induced mitochondrial delta psi m loss and caspase-3 activation, while the inhibition of caspase-3 by z-devd-fluoromethyl ketone (z-devd-fmk) only partially attenuates pkc delta activation and apoptosis. these data indicate that nsc606985-induced pkc delta activation is an early event upstream to mitochondrial delta psi m loss and caspase-3 activation, while activated caspase-3 has an amplifying effect on pkc delta proteolysis. in addition, nsc606985-induced apoptosis by pkc delta also involves caspase-3-independent mechanisms. taken together, our results suggest that nsc606985 is a potential agent for the treatment of aml. |
| WOS关键词 | ACUTE MYELOID-LEUKEMIA ; ETOPOSIDE-INDUCED APOPTOSIS ; ACUTE MYELOGENOUS LEUKEMIA ; ABL TYROSINE KINASE ; PKC-DELTA ; DNA-DAMAGE ; SUBCELLULAR-LOCALIZATION ; PROTEOLYTIC CLEAVAGE ; CASPASE ACTIVATION ; FLOW-CYTOMETRY |
| WOS研究方向 | Hematology |
| WOS类目 | Hematology |
| 语种 | 英语 |
| WOS记录号 | WOS:000228797400054 |
| 出版者 | AMER SOC HEMATOLOGY |
| URI标识 | http://www.irgrid.ac.cn/handle/1471x/2377682 |
| 专题 | 中国科学院大学 |
| 通讯作者 | Chen, GQ |
| 作者单位 | 1.Shanghai Med Univ 2, Dept Pathophysiol, Shanghai Inst Hematol, Rui Jin Hosp, Shanghai, Peoples R China 2.Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China 3.Chinese Acad Sci, Hlth Sci Ctr, Shanghai Inst Biol Sci, Shanghai, Peoples R China 4.Fudan Univ, Dept Hematol, Zhong Shan Hosp, Shanghai 200433, Peoples R China 5.Cornell Univ, Weill Med Coll, Dept Med Endocrinol, New York, NY USA |
| 推荐引用方式 GB/T 7714 | Song, MG,Gao, SM,Du, KM,et al. Nanomolar concentration of nsc606985, a camptothecin analog, induces leukernic-cell apoptosis through protein kinase c delta-dependent mechanisms[J]. Blood,2005,105(9):3714-3721. |
| APA | Song, MG.,Gao, SM.,Du, KM.,Xu, M.,Yu, Y.,...&Chen, GQ.(2005).Nanomolar concentration of nsc606985, a camptothecin analog, induces leukernic-cell apoptosis through protein kinase c delta-dependent mechanisms.Blood,105(9),3714-3721. |
| MLA | Song, MG,et al."Nanomolar concentration of nsc606985, a camptothecin analog, induces leukernic-cell apoptosis through protein kinase c delta-dependent mechanisms".Blood 105.9(2005):3714-3721. |
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来源：中国科学院大学
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