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Decitabine Downregulates TIGAR to Induce Apoptosis and Autophagy in Myeloid Leukemia Cells.
- Source :
-
Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2021 Jan 18; Vol. 2021, pp. 8877460. Date of Electronic Publication: 2021 Jan 18 (Print Publication: 2021). - Publication Year :
- 2021
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Abstract
- Decitabine (DAC) is a well-known DNA methyltransferase inhibitor, which has been widely used for the treatment of acute myeloid leukemia (AML). However, in addition to hypomethylation, DAC in AML is also involved in cell metabolism, apoptosis, and immunity. The TP53-induced glycolysis and apoptosis regulator (TIGAR) functions to inhabit glycolysis and protect cancer cells from reactive oxygen species- (ROS-) associated apoptosis. Our previous study revealed that TIGAR is highly expressed in myeloid leukemia cell lines and AML primary cells and associated with poor prognosis in adult patients with cytogenetically normal AML. In the present study, it was found that in a time- and concentration-dependent manner, DAC downregulates the TIGAR expression, induces ROS production, and promotes apoptosis in HL-60 and K562 cells. However, blocking the glycolytic pathway partially reversed the combined effects of DAC and TIGAR knockdown on apoptosis, ROS production, and cell cycle arrest, indicating that DAC induced apoptosis through the glycolytic pathway. Furthermore, TIGAR also has a negative impact on autophagy, while DAC treatment upregulates autophagy-related proteins LC3, Beclin-1, ATG3, and ATG-5, downregulates p62, and promotes the formation of autophagosomes, indicating that DAC may activate autophagy by downregulating TIGAR. Taken together, DAC plays an unmethylated role in inducing apoptosis and activating autophagy in myeloid leukemia by downregulating TIGAR.<br />Competing Interests: The authors declare that they have no conflict of interest.<br /> (Copyright © 2021 Lanzhu Li et al.)
- Subjects :
- Apoptosis drug effects
Apoptosis genetics
Apoptosis Regulatory Proteins metabolism
Autophagy drug effects
Autophagy genetics
Down-Regulation drug effects
Down-Regulation genetics
Gene Expression Regulation, Leukemic drug effects
Glycolysis drug effects
Glycolysis genetics
HL-60 Cells
Humans
K562 Cells
Phosphoric Monoester Hydrolases metabolism
Reactive Oxygen Species metabolism
Apoptosis Regulatory Proteins genetics
Decitabine pharmacology
Leukemia, Myeloid genetics
Leukemia, Myeloid metabolism
Leukemia, Myeloid pathology
Phosphoric Monoester Hydrolases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1942-0994
- Volume :
- 2021
- Database :
- MEDLINE
- Journal :
- Oxidative medicine and cellular longevity
- Publication Type :
- Academic Journal
- Accession number :
- 33532040
- Full Text :
- https://doi.org/10.1155/2021/8877460