Honokiol induces proteasomal degradation of AMLI-ETO oncoprotein via increasing ubiquitin conjugase UbcH8 expression in leukemia

doi:10.1016/j.bcp.2016.12.022

科研成果详情

题名	Honokiol induces proteasomal degradation of AMLI-ETO oncoprotein via increasing ubiquitin conjugase UbcH8 expression in leukemia
作者	Zhou, Bin 1; Li, Haiying 1; Xing, Chongyun2; Ye, Haige2; Feng, Jianhua2; Wu, Jianbo1; Lu, Zhongqiu3; Fang, Jing 4; Gao, Shenmeng1
发表日期	2017-03-15
发表期刊	BIOCHEMICAL PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Honokiol AMLI-ETO UbcH8
其他关键词	ACUTE MYELOID-LEUKEMIA ; HISTONE DEACETYLASE INHIBITORS ; RESIDUAL DISEASE DETECTION ; POLYMERASE-CHAIN-REACTION ; AML1-ETO FUSION PROTEIN ; CELL-CYCLE ARREST ; DEPENDENT DEGRADATION ; EPITHELIAL-CELLS ; CANCER PROGRAM ; APOPTOSIS
摘要	AMLI-ETO is the most common oncoprotein leading to acute myeloid leukemia (AML), in which 5-year survival rate is only about 30%. However, currently there are no specific therapies for AML patients with AML1-ETO. Here, we report that AMLI-ETO protein is rapidly degraded by Honokiol (HNK), a natural phenolic compound isolated from the plant Magnolia officinalis. HNK induced the degradation of AML1-ETO in a concentration-and time-dependent manner in leukemic cell lines and primary AML blasts with t (8;21) translocation. Mechanistically, HNK obviously increased the expression of UbcH8, an E2-conjugase for the degradation of AMLI-ETO, through triggering accumulation of acetylated histones in the promoter region of UbcH8. Knockdown of UbcH8 by small hairpin RNAs (shRNAs) prevented HNK-induced degradation of AML-ETO, suggesting that UbcH8 plays a critical role in the degradation of AMLI-ETO. HNK inhibited cell proliferation and induced apoptotic death without activation of caspase-3, which was reported to cleave and degrade AMLI-ETO protein. Thus, HNK-induced degradation of AML1-ETO is independent of activation of caspase-3. Finally, HNK reduced the angiogenesis and migration in Kasumi-1-injected zebrafish, decreased xenograft tumor size in a xenograft leukemia mouse model, and prolonged the survival time in mouse C1498 AML model. Collectively, HNK might be a potential treatment for t(8;21) leukemia by targeting AMLI-ETO oncoprotein. (C) 2016 Elsevier Inc. All rights reserved.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81501809, 81672087]; key construction academic subject (traditional Chinese medicine) of Zhejiang Province [2012-XK-A28]
出版者	PERGAMON-ELSEVIER SCIENCE LTD
出版地	OXFORD
ISSN	0006-2952
EISSN	1873-2968
卷号	128 页码:12-25
DOI	10.1016/j.bcp.2016.12.022
页数	14
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000395354800002
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	28043811
SCOPUSEID	2-s2.0-85008514433
通讯作者地址	[Gao, Shenmeng]Laboratory of Internal Medicine,The First Affiliated Hospital of Wenzhou Medical University,Shangcai Village, Nanbaixiang, Ouhai District,Wenzhou,China
Scopus学科分类	Biochemistry;Pharmacology
引用统计	被引频次：13[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/7684
专题	附属第一医院_血液内科第一临床医学院（信息与工程学院）、附属第一医院_急诊医学
通讯作者	Gao, Shenmeng
作者单位	1.Laboratory of Internal Medicine,The First Affiliated Hospital of Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China; 2.Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China; 3.Department of Emergency Medicine,The First Affiliated Hospital of Wenzhou Medical University,Nanbaixiang, Ouhai District,Wenzhou,325000,China; 4.Department of Drug Discovery and Biomedical Sciences,South Carolina College of Pharmacy,University of South Carolina,Columbia,United States
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhou, Bin,Li, Haiying,Xing, Chongyun,et al. Honokiol induces proteasomal degradation of AMLI-ETO oncoprotein via increasing ubiquitin conjugase UbcH8 expression in leukemia[J]. BIOCHEMICAL PHARMACOLOGY,2017,128:12-25.
APA	Zhou, Bin., Li, Haiying., Xing, Chongyun., Ye, Haige., Feng, Jianhua., ... & Gao, Shenmeng. (2017). Honokiol induces proteasomal degradation of AMLI-ETO oncoprotein via increasing ubiquitin conjugase UbcH8 expression in leukemia. BIOCHEMICAL PHARMACOLOGY, 128, 12-25.
MLA	Zhou, Bin,et al."Honokiol induces proteasomal degradation of AMLI-ETO oncoprotein via increasing ubiquitin conjugase UbcH8 expression in leukemia".BIOCHEMICAL PHARMACOLOGY 128(2017):12-25.