PMID- 32469848
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20210216
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 May 29
TI  - Nicotinamide Inhibits Glycolysis of HL-60 Cells by Modulating Sirtuin 1 
      (SIRT1)/Peroxisome Proliferator-Activated Receptor gamma Coactivator 1alpha 
      (PGC-1alpha)/Hypoxia-Inducible Factor-2alpha (HIF2alpha) Signaling Pathway.
PG  - e920810
LID - 10.12659/MSM.920810 [doi]
AB  - BACKGROUND Nicotinamide can affect differentiation and proliferation of leukemia 
      cells. This research aimed to explore the regulatory effect of nicotinamide on 
      glycolysis metabolism of leukemia cells and to clarify the associated mechanisms. 
      MATERIAL AND METHODS HL-60 cells were treated with nicotinamide and divided into 
      0.1, 1, and 10 mumol/l groups. HL-60 cells without any administration were 
      assigned as negative control (CT group). Glucolytic activity was evaluated by 
      detecting lactic acid production, and glucose level was measured using glucose 
      consumption assay. Apoptosis of HL-60 was examined using flow cytometry assay, 
      when cells were cultured for 24 h. Expressions of sirtuin 1 (SIRT1), peroxisome 
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), and 
      hypoxia-inducible factor-2alpha (HIF2alpha) were evaluated using a reverse 
      transcription PCR assay and Western blotting assay, respectively. RESULTS 
      Nicotinamide remarkably decreased lactic acid production and glucose levels in 
      leukemia cells compared with that of the CT group (p<0.05). Nicotinamide 
      significantly induced the apoptosis of HL-60 cells compared to that of the 
      negative control group (p<0.05). Nicotinamide significantly inhibited the 
      SIRT1/PGC-1alpha/HIF2alpha signaling pathway mRNAs compared to that of the CT 
      group (p<0.05). Nicotinamide remarkably reduced mitochondrial regulatory factors 
      SIRT1/PGC-1alpha expression compared to that in the CT group (p<0.05). 
      Nicotinamide obviously downregulated HIF2alpha compared with that of the CT group 
      (p<0.05). Moreover, all of the above nicotinamide-induced effects, including 
      glycolytic activity, apoptosis, and expression of SIRT1/PGC-1alpha/HIF2alpha, 
      were changed in a dose-dependent manner. CONCLUSIONS Nicotinamide can inhibit 
      glycolysis of HL-60 cells by inhibiting the mitochondrial regulatory factor 
      SIRT1/PGC-1alpha and suppressing transcription factor HIF2alpha.
FAU - Liu, Miao
AU  - Liu M
AD  - Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, 
      China (mainland).
FAU - Zhou, Pan
AU  - Zhou P
AD  - Hubei Medical Devices, Quality Supervision and Test Institute, Wuhan, Hubei, 
      China (mainland).
FAU - Li, Jiaojiao
AU  - Li J
AD  - Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, 
      China (mainland).
FAU - Jiang, Yi
AU  - Jiang Y
AD  - Department of Pediatrics, Renmin Hospital of Wuhan University, Wuhan, Hubei, 
      China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200529
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (PPAR gamma)
RN  - 0 (PPARGC1A protein, human)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Transcription Factors)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - 25X51I8RD4 (Niacinamide)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Gene Expression Regulation/genetics
MH  - HL-60 Cells/drug effects
MH  - Humans
MH  - Hypoxia/metabolism
MH  - Leukemia/*metabolism
MH  - Niacinamide/metabolism/*pharmacology
MH  - PPAR gamma/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/metabolism
MH  - Sirtuins/metabolism
MH  - Transcription Factors/metabolism
PMC - PMC7282349
COIS- Conflict of interest None.
EDAT- 2020/05/30 06:00
MHDA- 2021/02/17 06:00
PMCR- 2020/05/29
CRDT- 2020/05/30 06:00
PHST- 2020/05/30 06:00 [entrez]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/05/29 00:00 [pmc-release]
AID - 920810 [pii]
AID - 10.12659/MSM.920810 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 May 29;26:e920810. doi: 10.12659/MSM.920810.