ArticlePloS one2009
Acadesine kills chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review.Cells · 2021Pooled it
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Article
- Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis.Science advances · 2024Article
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
- Yangxinkang tablet protects against cardiac dysfunction and remodelling after myocardial infarction in rats through inhibition of AMPK/mTOR-mediated autophagy.Pharmaceutical biology · 2020Article
- Acadesine Circumvents Azacitidine Resistance in Myelodysplastic Syndrome and Acute Myeloid Leukemia.International journal of molecular sciences · 2019Article
- The ribonucleoside AICAr induces differentiation of myeloid leukemia by activating the ATR/Chk1 via pyrimidine depletion.The Journal of biological chemistry · 2019Article
- Review
- Metabolomics and proteomics identify the toxic form and the associated cellular binding targets of the anti-proliferative drug AICAR.The Journal of biological chemistry · 2019Article
- The roles of PKCs in regulating autophagy.Journal of cancer research and clinical oncology · 2018Review
- Implication and Regulation of AMPK during Physiological and Pathological Myeloid Differentiation.International journal of molecular sciences · 2018Review
- AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2.Neoplasia (New York, N.Y.) · 2018Article
- ATP-competitive Plk1 inhibitors induce caspase 3-mediated Plk1 cleavage and activation in hematopoietic cell lines.Oncotarget · 2018Article
- Impact of PKCε downregulation on autophagy in glioblastoma cells.BMC cancer · 2018Article
- Pan-Cancer Analysis Reveals the Functional Importance of Protein Lysine Modification in Cancer Development.Frontiers in genetics · 2018Article
- Article
- 5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells.Cell death discovery · 2017Article
- Article
- Energy disruptors: rising stars in anticancer therapy?Oncogenesis · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CML is an hematopoietic stem cell disease characterized by the t(9;22) (q34;q11) translocation encoding the oncoprotein p210BCR-ABL. The effect of acadesine (AICAR, 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside) a compound with known antileukemic effect on B cell chronic lymphoblastic leukemia (B-CLL) was investigated in different CML cell lines. Acadesine triggered loss of cell metabolism in K562, LAMA-84 and JURL-MK1 and was also effective in killing imatinib-resistant K562 cells and Ba/F3 cells carrying the T315I-BCR-ABL mutation. The anti-leukemic effect of acadesine did not involve apoptosis but required rather induction of autophagic cell death. AMPK knock-down by Sh-RNA failed to prevent the effect of acadesine, indicating an AMPK-independent mechanism. The effect of acadesine was abrogated by GF109203X and Ro-32-0432, both inhibitor of classical and new PKCs and accordingly, acadesine triggered relocation and activation of several PKC isoforms in K562 cells. In addition, this compound exhibited a potent anti-leukemic effect in clonogenic assays of CML cells in methyl cellulose and in a xenograft model of K562 cells in nude mice. In conclusion, our work identifies an original and unexpected mechanism by which acadesine triggers autophagic cell death through PKC activation. Therefore, in addition to its promising effects in B-CLL, acadesine might also be beneficial for Imatinib-resistant CML patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.