PMID- 38435444
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240305
IS  - 1726-6890 (Electronic)
IS  - 1735-0328 (Print)
IS  - 1726-6882 (Linking)
VI  - 22
IP  - 1
DP  - 2023 Jan-Dec
TI  - Glucose Metabolism in Acute Myeloid Leukemia Cell Line Is Regulated via 
      Combinational PI3K/AKT/mTOR Pathway Inhibitors.
PG  - e140507
LID - 10.5812/ijpr-140507 [doi]
LID - e140507
AB  - BACKGROUND: Metabolism reprogramming is a survival mechanism in acute myeloid 
      leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated 
      the effect of signaling pathway inhibitors on the expression of genes rewired in 
      the metabolic pathway of AML cells. METHODS: HL-60 cells were treated with 
      Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors 
      of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of 
      rapamycin (mTOR), either individually or in combination. The relative expressions 
      of glucose transporter 1, hexokinase 2, pyruvate kinase, pyruvate dehydrogenase 
      E1, citrate synthase, isocitrate dehydrogenase 2, and hypoxia inducible factor 1 
      subunit alpha were determined by real-time PCR. RESULTS: The combined treatment 
      of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression 
      of glucose transporter 1, hexokinase 2, pyruvate kinase M2, pyruvate 
      dehydrogenase E1, citrate synthase, isocitrate dehydrogenase 2, and hypoxia 
      inducible factor 1 subunit alpha. CONCLUSIONS: A combination of PI3K/AKT/mTOR 
      pathway inhibitors regulates the expression of genes involved in glycolysis, 
      pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and 
      interferes with metabolic reprogramming and immune evasion mechanisms of AML 
      leukemic cells. Combinational therapy approaches to block these pathways might be 
      a promising and novel therapeutic strategy for targeting the metabolic 
      requirements of AML cells.
CI  - Copyright (c) 2023, Ranjbar et al.
FAU - Ranjbar, Abbas
AU  - Ranjbar A
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
AD  - Student Research Committee, Mazandaran University of Medical Sciences, Sari, 
      Iran.
FAU - Soltanshahi, Mohsen
AU  - Soltanshahi M
AUID- ORCID: 0000-0003-1675-0765
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
AD  - Student Research Committee, Mazandaran University of Medical Sciences, Sari, 
      Iran.
FAU - Taghiloo, Saeid
AU  - Taghiloo S
AUID- ORCID: 0000-0002-8813-6046
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
FAU - Asgarian-Omran, Hossein
AU  - Asgarian-Omran H
AUID- ORCID: 0000-0003-3816-8792
AD  - Department of Immunology, School of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
AD  - Gastrointestinal Cancer Research Center, Non-Communicable Diseases Institute, 
      Mazandaran University of Medical Sciences, Sari, Iran.
LA  - eng
PT  - Journal Article
DEP - 20231114
PL  - Netherlands
TA  - Iran J Pharm Res
JT  - Iranian journal of pharmaceutical research : IJPR
JID - 101208407
PMC - PMC10909123
OTO - NOTNLM
OT  - Acute Myeloid Leukemia
OT  - Citric Acid Cycle
OT  - Glycolysis
OT  - PI3K/AKT/mTOR
OT  - Signaling Pathways
COIS- The authors declare that they have no conflict of interest concerning the 
      contents of this article.
EDAT- 2024/03/04 06:46
MHDA- 2024/03/04 06:47
PMCR- 2023/11/14
CRDT- 2024/03/04 05:01
PHST- 2023/09/05 00:00 [received]
PHST- 2023/10/09 00:00 [revised]
PHST- 2023/10/10 00:00 [accepted]
PHST- 2024/03/04 06:47 [medline]
PHST- 2024/03/04 06:46 [pubmed]
PHST- 2024/03/04 05:01 [entrez]
PHST- 2023/11/14 00:00 [pmc-release]
AID - 10.5812/ijpr-140507 [doi]
PST - epublish
SO  - Iran J Pharm Res. 2023 Nov 14;22(1):e140507. doi: 10.5812/ijpr-140507. 
      eCollection 2023 Jan-Dec.