PMID- 23469683
OWN - NLM
STAT- MEDLINE
DCOM- 20130408
LR  - 20211203
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 68
IP  - 2
DP  - 2013 Feb
TI  - Combination therapy with 5-amino-4-imidazolecarboxamide riboside and arsenic 
      trioxide in acute myeloid leukemia cells involving AMPK/TSC2/mTOR pathway.
PG  - 117-23
AB  - The aim of this study was to demonstrate the effects of the AMP-activated protein 
      kinase (AMPK) activator 5-amino-4-imidazolecarboxamide riboside (AICAR) in 
      combination with arsenic trioxide (ATO) in acute myeloid leukemia cells and 
      determine its mechanism of action. Cell lines were either exposed to each drug 
      alone or both the drugs simultaneously. Cell proliferation, cell cycle and 
      apoptosis were assessed. Combination index (CI) method was used to calculate the 
      synergistic, additive, or antagonistic effects of these drugs. Western blot 
      technique was used to study the signaling molecules in the AMPK/TSC2/mTOR 
      pathway. Simultaneous exposure of HL-60 cells to AICAR and ATO indicated a 
      synergism (CI < 1), whereas CI on NB4 cells was greater than 1. In HL-60, the 
      change in expression level of each protein was quite significant in the presence 
      of the combination as compared to that induced through any single agent. On the 
      contrary, ATO weakened the effect of AICAR-mediated AMPK activation in NB4 cells. 
      ATO caused a profound decrease in the protein level of PML/RARalpha in NB4 cells 
      after 48 h, but there was no change with AICAR and the combination. The 
      combination of AICAR and ATO produced a synergistic effect in the treatment of 
      HL-60 cells involving AMPK/TSC2/mTOR pathway, and AICAR reduced ATO-mediated 
      apoptotic death on acute promyelocytic leukemia NB4 cells.
FAU - Chen, Lan
AU  - Chen L
AD  - Department of Pediatrics, the Second Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Han, Fengtong
AU  - Han F
FAU - Qu, Hui
AU  - Qu H
FAU - Yan, Hongji
AU  - Yan H
FAU - Ren, Lihong
AU  - Ren L
FAU - Yang, Shufen
AU  - Yang S
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Arsenicals)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Oxides)
RN  - 0 (RARA protein, human)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoic Acid Receptor alpha)
RN  - 0 (Ribonucleotides)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
RN  - S7V92P67HO (Arsenic Trioxide)
SB  - IM
MH  - AMP-Activated Protein Kinases/*physiology
MH  - Aminoimidazole Carboxamide/*analogs & derivatives/therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - Apoptosis/drug effects
MH  - Arsenic Trioxide
MH  - Arsenicals/*therapeutic use
MH  - Blotting, Western
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival
MH  - Drug Synergism
MH  - HL-60 Cells
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Leukemia, Myeloid, Acute/*drug therapy/pathology
MH  - Oxides/*therapeutic use
MH  - Receptors, Retinoic Acid/biosynthesis
MH  - Retinoic Acid Receptor alpha
MH  - Ribonucleotides/*therapeutic use
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*physiology
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*physiology
EDAT- 2013/03/09 06:00
MHDA- 2013/04/09 06:00
CRDT- 2013/03/09 06:00
PHST- 2013/03/09 06:00 [entrez]
PHST- 2013/03/09 06:00 [pubmed]
PHST- 2013/04/09 06:00 [medline]
PST - ppublish
SO  - Pharmazie. 2013 Feb;68(2):117-23.