Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappa B and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner
Wang, L.; Zhao, W. -L.; Yan, J. -S.; Liu, P.; Sun, H. -P.; Zhou, G. -B.; Weng, Z. -Y.; Wu, W. -L.; Weng, X. -Q.; Sun, X. -J.; Chen, Z.; Sun, H. -D.; Chen, S. -J.
通讯作者Sun, HD (reprint author), Shanghai Jiao Tong Univ, Rui Jin Hosp, Sch Med, Shanghai Inst Hematol,State Key Lab Med Genom, 197 Rui Jin Er Rd, Shanghai 200025, Peoples R China. hdsun@mail.kib.ac.cn ; sjchen@stn.sh.cn
2007-02-01
发表期刊CELL DEATH AND DIFFERENTIATION
ISSN1350-9047
卷号14期号:2页码:306-317
摘要Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-X-L downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappa B inactivation by preventing NF-kappa B nuclear translocation and inducing I kappa B alpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8; 21) leukemia blasts and caused AML1-ETO degradation. In murine t(8; 21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8; 21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.
关键词Eriocalyxin b Acute Myeloid Leukemia Apoptosis Nf-kappa b Mapk Aml1-eto
学科领域Biochemistry & Molecular Biology ; Cell Biology
DOI10.1038/sj.cdd.4401996
收录类别SCI
语种英语
WOS记录号WOS:000243493000011
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/15410
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Shanghai Jiao Tong Univ, Rui Jin Hosp, Sch Med, Shanghai Inst Hematol,State Key Lab Med Genom, Shanghai 200025, Peoples R China
2.Shanghai Jiao Tong Univ, Inst Biol Sci, Inst Hlth Sci, Shanghai 200025, Peoples R China
3.Chinese Acad Sci, Grad Sch, Shanghai 200025, Peoples R China
4.Chinese Acad Sci, Kunming Int Bot, Kunming 650204, Yunnan, Peoples R China
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Wang, L.,Zhao, W. -L.,Yan, J. -S.,et al. Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappa B and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner[J]. CELL DEATH AND DIFFERENTIATION,2007,14(2):306-317.
APA Wang, L..,Zhao, W. -L..,Yan, J. -S..,Liu, P..,Sun, H. -P..,...&Chen, S. -J..(2007).Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappa B and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.CELL DEATH AND DIFFERENTIATION,14(2),306-317.
MLA Wang, L.,et al."Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappa B and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner".CELL DEATH AND DIFFERENTIATION 14.2(2007):306-317.
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