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Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo

文献类型：期刊论文

作者Hu, Liangning1; Wu, Huiqun1; Li, Bo2; Song, Dongliang1; Yang, Guang1; Chen, Gege1; Xie, Bingqian1; Xu, Zhijian2; Zhang, Yong2; Yu, Dandan1
刊名ACTA BIOCHIMICA ET BIOPHYSICA SINICA
出版日期2017-05
卷号49期号:5页码:420-427
关键词dihydrocelastrol multiple myeloma apoptosis
ISSN号1672-9145
DOI10.1093/abbs/gmx021
文献子类Article
英文摘要Multiple myeloma (MM) is the second most frequent malignant hematological disease. Dihydrocelastrol (DHCE) is synthesized by hydrogenated celastrol, a treterpene isolated from Chinese medicinal plant Tripterygium regelii. In this study, we first reported the anti-tumor activity of DHCE on MM cells. We found that DHCE could inhibit cell proliferation and promote apoptosis through caspase-dependent way in vitro. In addition, DHCE could inactivate the expression of interleukin (IL)-6 and downregulate the phosphorylation of extracellular regulated protein kinases (ERK1/2) and the signal transducer and activator of transcription 3 (STAT3) in MM. It also retained its activity against MM cell lines in the presence of IL-6. Furthermore, treatment of MM cells with DHCE resulted in an accumulation of cells in G(0)/G(1) phase of the cell cycle. Notably, DHCE reduced the expression of cyclin D1 and cyclin-dependent kinases 4 and 6 in MM cell lines. Additionally, its efficacy toward the MM cell lines could be enhanced in combination with the histone deacetylase inhibitor panobinostat (LBH589), which implied the possibility of the combination treatment of DHCE and LBH589 as a potential therapeutic strategy in MM. In addition, treatment of NCI-H929 tumor-bearing nude mice with DHCE (10 mg/kg/d, i.p., 1-14 days) resulted in 73% inhibition of the tumor growth in vivo. Taken together, the results of our present study indicated that DHCE could inhibit cellular proliferation and induce cell apoptosis in myeloma cells mediated through different mechanisms, possibly through inhibiting the IL-6/STAT3 and ERK1/2 pathways. And it may provide a new therapeutic option for MM patients.
WOS关键词HEAT-SHOCK RESPONSE ; PROTEASOME INHIBITOR ; DRUG-COMBINATION ; CELASTROL ; CANCER ; GROWTH ; DEATH ; PERSPECTIVES ; BORTEZOMIB ; MICE
资助项目National Natural Science Foundation of China[81570190] ; National Natural Science Foundation of China[81372391] ; National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[31271496] ; State Key Laboratory of Bioactive Substance and Function of Natural Medicines[GTZK201606]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
CSCD记录号CSCD:6071989
WOS记录号WOS:000400889300005
出版者OXFORD UNIV PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/272684]  
专题药物发现与设计中心
通讯作者Tao, Yi; Shi, Jumei; Zhu, Weiliang
作者单位1.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Hematol, Shanghai 200072, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
3.Tongji Univ, Coll Life Sci & Technol, Shanghai 200092, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Liangning,Wu, Huiqun,Li, Bo,et al. Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2017,49(5):420-427.
APA Hu, Liangning.,Wu, Huiqun.,Li, Bo.,Song, Dongliang.,Yang, Guang.,...&Zhu, Weiliang.(2017).Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,49(5),420-427.
MLA Hu, Liangning,et al."Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 49.5(2017):420-427.

入库方式： OAI收割

来源：上海药物研究所

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