Evidence map›Paper›PMID 38204257›Full record

ArticleAnti-cancer agents in medicinal chemistry2024

Combination of Ethacrynic Acid and ATRA Triggers Differentiation and/or Apoptosis of Acute Myeloid Leukemia Cells through ROS.

Lu Li, Hui-Min Xi, Hao Lu, Xun Cai

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Article in Anti-cancer agents in medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Significance of Vitamins A and E in Cancer Progression and Prevention.International journal of molecular sciences · 2025
    Review
  3. Review
  4. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Lu LiState Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197 Ruijin Road II, Shanghai, 200025, China.
Hui-Min XiState Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197 Ruijin Road II, Shanghai, 200025, China.
Hao LuState Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197 Ruijin Road II, Shanghai, 200025, China.
Xun CaiState Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197 Ruijin Road II, Shanghai, 200025, China.ORCID 0000-0003-4372-8889

Funding

Natural Science Foundation of Shanghai 17ZR1417100
6 · The paper itself

Abstract

BACKGROUND AND

objectiveAll-trans retinoic acid (ATRA), an effective differentiation inducer, has been applied clinically to treat acute promyelocytic leukemia (APL). Unfortunately, it is not as potent in other kinds of acute myeloid leukemia (AML). Ethacrynic acid (EA), a classical powerful diuretic, can increase reactive oxygen species (ROS) contents, which can assist ATRA in inducing differentiation in AML cells. Here, we investigated the effect of EA combined with ATRA (EA+RA) on some AML cells except APL.

methodsApoptosis and differentiation were determined by morphology, cell viability, Annexin-V assay and CD11c expression. Western blot analysis and the detection of ROS and mitochondrial transmembrane potentials (MMP) were used to investigate the mechanisms.

resultsAML cells exhibited differentiation and/or apoptosis after EA+RA treatment. EA+RA increased the intracellular ROS contents. EA+RA-induced apoptosis was accompanied by MMP attenuation and caspase-3/7 activation. EA+RA-induced differentiation was along with MEK/ERK and Akt activation and increased expression of PU.1, CCAAT/enhancer-binding protein β (C/EBPβ) and C/EBPε. N-acetyl-L-cysteine (NAC), an antioxidant, thoroughly reduced EA+RA-increased ROS, and also inhibited MMP attenuation, the activation of caspase- 3/7, MEK/ERK and Akt pathways, the elevation of PU.1 and C/EBPs, and apoptosis and differentiation. However, MEK or PI3K specific inhibitors only suppressed EA+RA-triggered differentiation and the elevation of PU.1 and C/EBPs, but not ROS levels.

conclusionEA+RA induced cell apoptosis through ROS dependent MMP attenuation and caspase 3/7 activation while inducing differentiation by ROS-MEK/ERK-PU.1/C/EBPs and ROS-Akt-PU.1/C/EBPs pathways. In summary, it may provide innovative ATRA-based combination therapy strategies for AML patients

Indexed as

Antineoplastic AgentsApoptosisCell DifferentiationDrug Screening Assays, AntitumorEthacrynic AcidLeukemia, Myeloid, AcuteReactive Oxygen SpeciesTretinoinCell ProliferationCell SurvivalDose-Response Relationship, DrugHumansMolecular StructureStructure-Activity RelationshipTumor Cells, CulturedAntineoplastic AgentsEthacrynic AcidReactive Oxygen SpeciesTretinoinacute myeloid leukemiaAll-trans retinoic acidapoptosisdifferentiation.ethacrynic acidreactive oxygen species

Identifiers

PMID38204257

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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.