AICAr suppresses cell proliferation by inducing NTP and dNTP pool imbalances in acute lymphoblastic leukemia cells

@article{Du2019AICArSC,
  title={AICAr suppresses cell proliferation by inducing NTP and dNTP pool imbalances in acute lymphoblastic leukemia cells},
  author={Lijuan Du and Fan Yang and Houshun Fang and Huiying Sun and Yao Chen and Yan Xu and Hui Li and Liang Zheng and Bin-Bing Stephen Zhou},
  journal={The FASEB Journal},
  year={2019},
  volume={33},
  pages={4525 - 4537}
}
It has been shown that 5‐amino‐4‐imidazolecarboxamide riboside (AICAr) can inhibit cell proliferation and induce apoptosis in childhood acute lymphoblastic leukemia (ALL) cells. Although AICAr could regulate cellular energy metabolism by activating AMPK, the cytotoxic mechanisms of AICAr are still unclear. Here, we knocked out TP53 or PRKAA1 gene (encoding AMPKα1) in NALM‐6 and Reh cells by using the clustered regularly interspaced short palindromic repeats/Cas9 system and found that AICAr… Expand
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The ribonucleoside AICAr induces differentiation of myeloid leukemia by activating the ATR/Chk1 via pyrimidine depletion
TLDR
An AMPK-independent effect of AICAr is delineated on myeloid leukemia differentiation that involves perturbation of pyrimidine biosynthesis and activation of the DNA damage response network. Expand
Metabolomics Identifies Pyrimidine Starvation as the Mechanism of 5-Aminoimidazole-4-Carboxamide-1-β-Riboside-Induced Apoptosis in Multiple Myeloma Cells
TLDR
Pyrimidine biosynthesis is identified as a potential molecular target for future therapeutics in multiple myeloma cells after apoptosis was induced by limiting DNA synthesis rather than RNA synthesis and phosphorylation of AICAr by adenosine kinase was required. Expand
Metabolomics Identi fi es Pyrimidine Starvation as the Mechanism of 5-Aminoimidazole-4-Carboxamide-1-b-Riboside-Induced Apoptosis in Multiple Myeloma Cells
To investigate the mechanism by which 5-aminoimidazole-4-carboxamide-1-b-riboside (AICAr) induces apoptosis in multiple myeloma cells, we conducted an unbiased metabolomics screen. AICAr hadExpand
AICAR induces apoptosis independently of AMPK and p53 through up-regulation of the BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia cells.
TLDR
The notion that AICAR is an interesting alternative therapeutic option for CLL patients with impaired p53 function and resistance to conventional chemotherapy is supported. Expand
5-Aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved.
TLDR
The results indicate that AICAriboside induces apoptosis independently of ZMP synthesis and AMPK activation in Jurkat cells. Expand
5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside Inhibits Cancer Cell Proliferation in Vitro and in Vivo via AMP-activated Protein Kinase*
TLDR
Results indicate that AICAR can be utilized as a therapeutic drug to inhibit cancer, and AMPK can be a potential target for treatment of various cancers independent of the functional tumor suppressor gene, LKB. Expand
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It is demonstrated that AICA riboside promotes apoptosis in undifferentiated human neuroblastoma cells (SH-SY5Y), inducing a raise in caspase-3 activity, raising the intriguing clue that the neurotoxic effect of AICA Riboside on the developing brain might contribute to the neurological manifestations of syndromes related to purine dismetabolisms. Expand
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TLDR
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