Document Detail


Inhibition of adenosine monophosphate-activated protein kinase induces apoptosis in multiple myeloma cells.
MedLine Citation:
PMID:  17351392     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we show that adenosine monophosphate-activated protein kinase (AMPK) is expressed and activated in multiple myeloma cells. The inhibition of AMPK induced growth arrest and reduction of cell viability in the cell viability assay using the water-soluble tetrazolium salt 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay). Induction of apoptosis was determined by annexin-V and propidium iodide staining. The prevention of apoptosis using the pancaspase inhibitor ZVAD-fmk and caspase-3 cleavage upon incubation with the AMPK inhibitor (AMPKI) is shown. Furthermore, incubation of myeloma cells with AMPKI resulted in the downregulation of pAMPK, Mcl-1 and Bcl-xL. Coincubation of AMPKI and melphalan led to a strong additional increase of apoptosis in myeloma cells. We conclude that AMPKI has a strong antimyeloma activity in vitro and represents a new targeted strategy in the treatment of multiple myeloma.
Authors:
Philipp Baumann; Sonja Mandl-Weber; Bertold Emmerich; Christian Straka; Ralf Schmidmaier
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anti-cancer drugs     Volume:  18     ISSN:  0959-4973     ISO Abbreviation:  Anticancer Drugs     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-12     Completed Date:  2007-04-25     Revised Date:  2008-07-09    
Medline Journal Info:
Nlm Unique ID:  9100823     Medline TA:  Anticancer Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  405-10     Citation Subset:  IM    
Affiliation:
Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum der Universität München, Germany. Philipp.Baumann@med.uni-muenchen.de
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MeSH Terms
Descriptor/Qualifier:
Annexins / biosynthesis
Antineoplastic Agents*
Antineoplastic Agents, Alkylating / pharmacology
Apoptosis / drug effects*
Blotting, Western
Brain Neoplasms / drug therapy*,  pathology
Cell Survival / drug effects
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
Down-Regulation / drug effects
Enzyme Inhibitors / pharmacology*
Humans
Indicators and Reagents
Melphalan / pharmacology
Multiple Myeloma / drug therapy*,  pathology
Neoplasm Proteins / biosynthesis
Proto-Oncogene Proteins c-bcl-2 / biosynthesis
bcl-X Protein / biosynthesis
Chemical
Reg. No./Substance:
0/Annexins; 0/Antineoplastic Agents; 0/Antineoplastic Agents, Alkylating; 0/Enzyme Inhibitors; 0/Indicators and Reagents; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein; 0/myeloid cell leukemia sequence 1 protein; 148-82-3/Melphalan; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

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


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