Document Detail


Effect of artesunate on inhibiting proliferation and inducing apoptosis of SP2/0 myeloma cells through affecting NFkappaB p65.
MedLine Citation:
PMID:  19728025     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The initial treatment of multiple myeloma (MM) experienced a paradigm shift, in the past decade, with the introduction of novel agents such as thalidomide, lenalidomide and bortezomib, leading to improved outcomes. High dose therapy and autologous stem cell transplantation remain an important therapeutic option for patients with MM eligible for the procedure. However, most of these treatment regimens are too expensive for Chinese patients. Therefore, we investigated the effects of artesunate, which is commonly used in the treatment of severe malaria, on inhibition of proliferation and induction of apoptosis of a mouse myeloma cell line SP2/0. The growth inhibition of SP2/0 cell proliferation induced by artesunate (ART) treatment was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and the rate of apoptosis and cell cycle changes induced by ART were analyzed by flow cytometry. ART-induced morphology changes of apoptosis in SP2/0 cells, as observed by light and transmission electron microscopy. Additionally, DNA laddering, which is a hallmark of apoptosis, was observed by agarose gel electrophoresis of DNA harvested from SP2/0 cells treated with ART. The levels of nuclear factor kappa B p65 (NFkappaB p65) protein in nucleus and the inhibitor of NFkappaB (IkappaBalpha) in the cytoplasm were measured by western blot analysis and ELISA to evaluate NFkappaB p65 transcription activity indirectly. The results show that artesunate inhibited the proliferation and induced apoptosis of SP2/0 cells in a dose- and time-dependent manner. Artesunate also increased the proportion of SP2/0 cells in G0/G1 phase, while decreased the proportion of cells in G2/M or S phase. Additionally, artesunate treatment decreased the level of NFkappaB p65 protein in the nucleus, while increased the level of IkappaBalpha protein in the cytoplasm. The present result is the first report to show that artesunate may be useful in the treatment of MM.
Authors:
Shihui Li; Fang Xue; Zhiyong Cheng; Xiaoyang Yang; Suyun Wang; Fengyong Geng; Ling Pan
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Publication Detail:
Type:  Journal Article     Date:  2009-08-29
Journal Detail:
Title:  International journal of hematology     Volume:  90     ISSN:  1865-3774     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-04-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  513-21     Citation Subset:  IM    
Affiliation:
Department of Hematology, The Second Hospital of Hebei Medical University, 215, Heping Xi Road, 050000 Shijiazhuang City, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Artemisinins / pharmacology*
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Shape / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor / methods
Mice
Mice, Inbred BALB C
Multiple Myeloma / metabolism,  pathology*
Neoplasm Transplantation
Proteins / metabolism
Time Factors
Transcription Factor RelA / metabolism*
Tumor Burden / drug effects
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Artemisinins; 0/IkappaBNS protein, mouse; 0/Proteins; 0/Rela protein, mouse; 0/Transcription Factor RelA; 83507-69-1/artesunate

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


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