Document Detail


Arsenic trioxide and 2-methoxyestradiol reduce beta-catenin accumulation after proteasome inhibition and enhance the sensitivity of myeloma cells to Bortezomib.
MedLine Citation:
PMID:  18485479     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Beta-catenin, the key protein in canonical Wingless/int (Wnt) pathway, degrades via ubiquitin-proteasome pathway. Recently, it proved important roles in the proliferation of myeloma cells. But little is known about whether cytoplasmic beta-catenin content is associated with myeloma cell's sensitivity to Bortezomib. We examined the constitutive expression of beta-catenin in five myeloma cell lines and primary cells from patients. Meanwhile, the effect of Bortezomib combined with arsenic trioxide (As(2)O(3))/2-methoxyestradiol (2ME2) on beta-catenin accumulation, myeloma cells' survival, apoptosis and their sensitivity to Bortezomib were also investigated. Our study proved that beta-catenin protein levels are negatively associated with myeloma cells' sensitivity to Bortezomib. As(2)O(3)/2ME2 can reduce cytoplasmic beta-catenin accumulation after proteasome inhibition and enhance myeloma cells' sensitivity to Bortezomib. This will preliminarily help to optimize the new therapeutic regimens for MM treatment in the future.
Authors:
Lili Zhou; Jian Hou; Weijun Fu; Dongxing Wang; Zhenggang Yuan; Hua Jiang
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Publication Detail:
Type:  Journal Article     Date:  2008-05-15
Journal Detail:
Title:  Leukemia research     Volume:  32     ISSN:  0145-2126     ISO Abbreviation:  Leuk. Res.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-07-23     Completed Date:  2008-10-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1674-83     Citation Subset:  IM    
Affiliation:
Department of Hematology, the Second Affiliated Hospital to the Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Apoptosis / drug effects
Arsenicals / administration & dosage
Blotting, Western
Boronic Acids / administration & dosage
Cell Proliferation / drug effects
Drug Therapy, Combination
Enzyme-Linked Immunosorbent Assay
Estradiol / administration & dosage,  analogs & derivatives
Gene Expression Regulation, Neoplastic / drug effects*
Humans
Multiple Myeloma / drug therapy*,  metabolism,  pathology
Oxides / administration & dosage
Proteasome Endopeptidase Complex / antagonists & inhibitors*
Pyrazines / administration & dosage
RNA, Messenger / metabolism
RNA, Small Interfering / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
beta Catenin / genetics*
Chemical
Reg. No./Substance:
0/Arsenicals; 0/Boronic Acids; 0/CTNNB1 protein, human; 0/Oxides; 0/Pyrazines; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/beta Catenin; 0/bortezomib; 1327-53-3/arsenic trioxide; 362-07-2/2-methoxyestradiol; 50-28-2/Estradiol; EC 3.4.25.1/Proteasome Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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