| Inhibition of adenosine monophosphate-activated protein kinase induces apoptosis in multiple myeloma cells. | |
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MedLine Citation:
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PMID: 17351392 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Philipp Baumann; Sonja Mandl-Weber; Bertold Emmerich; Christian Straka; Ralf Schmidmaier |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Anti-cancer drugs Volume: 18 ISSN: 0959-4973 ISO Abbreviation: Anticancer Drugs Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-12 Completed Date: 2007-04-25 Revised Date: 2008-07-09 |
Medline Journal Info:
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Nlm Unique ID: 9100823 Medline TA: Anticancer Drugs Country: England |
Other Details:
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Languages: eng Pagination: 405-10 Citation Subset: IM |
Affiliation:
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Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum der Universität München, Germany. Philipp.Baumann@med.uni-muenchen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Annexins
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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:
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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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