Inhibition of adenosine monophosphate-activated protein kinase induces apoptosis in multiple myeloma cells

• Published in: Anti-cancer drugs Vol. 18; no. 4; p. 405
• Main Authors: Baumann, Philipp, Mandl-Weber, Sonja, Emmerich, Bertold, Straka, Christian, Schmidmaier, Ralf
• Format: Journal Article
• Language: English
• Published: England 01.04.2007
• Subjects: Annexins - biosynthesis; Antineoplastic Agents; Antineoplastic Agents, Alkylating - pharmacology; Apoptosis - drug effects; bcl-X Protein - biosynthesis; Blotting, Western; Brain Neoplasms - drug therapy; Brain Neoplasms - 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; Multiple Myeloma - pathology; Myeloid Cell Leukemia Sequence 1 Protein; Neoplasm Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis
• ISSN: 0959-4973; 1473-5741
• DOI: 10.1097/cad.0b013e32801416b6

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.