PMID- 17669398
OWN - NLM
STAT- MEDLINE
DCOM- 20071105
LR  - 20211203
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 313
IP  - 16
DP  - 2007 Oct 1
TI  - Activation of adenosine monophosphate activated protein kinase inhibits growth of 
      multiple myeloma cells.
PG  - 3592-603
AB  - The role of adenosine monophosphate activated protein kinase (AMPK) in regulating 
      multiple myeloma (MM) cell growth is not yet clear. In this study, we show that 
      the AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAr) and D942 
      inhibit cell growth in MM cell lines. AICAr also induced an S-phase cell cycle 
      arrest in all four tested cell lines and led to phosphorylation and thus 
      activation of AMPK. Furthermore, the inhibition of a nucleoside transporter by 
      nitrobenzyl-thio-9-beta-d-ribofuranosylpurine (NBTI), inhibition of the adenosine 
      kinase by iodotubericidine and inhibition of AMPK by AMPKI Compound C reversed 
      AICAr effects, indicating that the cellular effects of AICAr were mediated by 
      AMPK. Activation of AMPK inhibited basal extracellular signal-regulated kinase 
      (ERK), mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) as well as 
      AKT phosphorylation, and blocked IL-6, IGF-1, and HS-5 stromal cell conditioned 
      medium-induced increase of cell growth. Troglitazone, which has previously been 
      shown to activate AMPK, similarly inhibited MM cell growth, activated AMPK, and 
      decreased ERK and P70S6K phosphorylation. Our results suggest that activation of 
      AMPK inhibits MM cell growth despite stimulation with IL-6, IGF-1, or HS-5 
      stromal cell conditioned medium and represents a potential new target in the 
      therapy of MM.
FAU - Baumann, Philipp
AU  - Baumann P
AD  - Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum 
      der Universitat Munchen, Germany. philipp.baumann@med.uni-muenchen.de
FAU - Mandl-Weber, Sonja
AU  - Mandl-Weber S
FAU - Emmerich, Bertold
AU  - Emmerich B
FAU - Straka, Christian
AU  - Straka C
FAU - Schmidmaier, Ralf
AU  - Schmidmaier R
LA  - eng
PT  - Journal Article
DEP - 20070704
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Chromans)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-6)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Ribonucleotides)
RN  - 0 (Thiazolidinediones)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - AMP-Activated Protein Kinases
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Chromans/pharmacology
MH  - Culture Media, Conditioned
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Interleukin-6/pharmacology
MH  - Multienzyme Complexes/*metabolism
MH  - Multiple Myeloma/*enzymology/*pathology
MH  - Phosphorylation/drug effects
MH  - Protein Kinases/metabolism
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Ribonucleotides/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - S Phase/drug effects
MH  - Signal Transduction/drug effects
MH  - Stromal Cells/drug effects
MH  - TOR Serine-Threonine Kinases
MH  - Thiazolidinediones/pharmacology
MH  - Troglitazone
EDAT- 2007/08/03 09:00
MHDA- 2007/11/06 09:00
CRDT- 2007/08/03 09:00
PHST- 2007/03/08 00:00 [received]
PHST- 2007/06/14 00:00 [revised]
PHST- 2007/06/15 00:00 [accepted]
PHST- 2007/08/03 09:00 [pubmed]
PHST- 2007/11/06 09:00 [medline]
PHST- 2007/08/03 09:00 [entrez]
AID - S0014-4827(07)00279-0 [pii]
AID - 10.1016/j.yexcr.2007.06.020 [doi]
PST - ppublish
SO  - Exp Cell Res. 2007 Oct 1;313(16):3592-603. doi: 10.1016/j.yexcr.2007.06.020. Epub 
      2007 Jul 4.