Evidence map›Paper›PMID 24887205›Full record

ArticleJournal of experimental & clinical cancer research : CR2014

Arsenic trioxide induces oxidative stress, DNA damage, and mitochondrial pathway of apoptosis in human leukemia (HL-60) cells.

Sanjay Kumar, Clement G Yedjou, Paul B Tchounwou

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
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

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.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 154 citations in OpenAlex.

  1. Article
  2. Distinct CaArchives of toxicology · 2026
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  3. Review
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  5. Oxeiptosis - potential in cancer treatment?Expert reviews in molecular medicine · 2026
    Review
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  8. Arsenome, Arsenobolome, and Arsenobiolome.International journal of molecular sciences · 2025
    Review
  9. Article
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  11. Article
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  13. Article
  14. Article
  15. Article
  16. Article
  17. A Leukemic Target with a Thousand Faces: The Mitochondria.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Mechanistic update of Trisenox in blood cancer.Current research in pharmacology and drug discovery · 2023
    Review
  20. Review

14 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Sanjay Kumar
Clement G Yedjou
Paul B TchounwouCellomics and Toxicogenomics Research Laboratory, NIH/NIMHD-RCMI Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lunch Street, Box18750, Jackson, Mississippi MS39217, USA. paul.b.tchounwou@jsums.edu.
Jackson State University · US

Funding

RCMI-Center for Environmental HealthG12MD007581 · NIMHD · JACKSON STATE UNIVERSITY · PI TCHOUNWOU, PAUL B. · 2012 to 2017
$11.2M
NIMHD NIH HHS G12 MD007581NIMHD NIH HHS G12MD007581
6 · The paper itself

Abstract

backgroundAcute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), which accounts for approximately 10% of all acute myloid leukemia cases. It is a blood cancer that is formed by chromosomal mutation. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Arsenic trioxide (ATO) has been used successfully for treatment of APL patients, and both induction and consolidated therapy have resulted in complete remission. Recently published studies from our laboratory have demonstrated that ATO pharmacology as an anti-leukemic drug is associated with cytotoxic and genotoxic effects in leukemia cells.

methodsIn the present study, we further investigated the detailed molecular mechanism of ATO-mediated intrinsic pathway of apoptosis; using HL-60 cells as a test model. Oxidative stress was assessed by spectrophotometric measurements of MDA and GSH levels while genotoxicity was determined by single cell gel electrophoresis (Comet assay). Apoptosis pathway was analyzed by Western blot analysis of Bax, Bcl2 and caspase 3 expression, as well as immunocytochemistry and confocal imaging of Bax and Cyt c translocation and mitochondrial membrane potential depolarization.

resultsATO significantly (p < 0.05) induces oxidative stress, DNA damage, and caspase 3 activity in HL-60 cells in a dose-dependent manner. It also activated the intrinsic pathway of apoptosis by significantly modulating (p < 0.05) the expression and translocation of apoptotic molecules and decreasing the mitochondrial membrane potential in leukemia cells.

conclusionTaken together, our research demonstrated that ATO induces mitochondrial pathway of apoptosis in HL-60 cells. This apoptotic signaling is modulated via oxidative stress, DNA damage, and change in mitochondrial membrane potential, translocation and upregulation of apoptotic proteins leading programmed cell death.

Indexed as

ApoptosisDNA DamageOxidative StressAntineoplastic AgentsApoptosis Regulatory ProteinsArsenicalsArsenic Trioxidebcl-2-Associated X ProteinCaspase 3Cytochromes cDrug Screening Assays, AntitumorGlutathioneHL-60 CellsHumansLeukemia, Promyelocytic, AcuteLipid PeroxidationAntineoplastic AgentsApoptosis Regulatory ProteinsArsenicalsArsenic TrioxideBAX protein, humanbcl-2-Associated X ProteinCASP3 protein, humanCaspase 3Cytochromes cGlutathioneOxides

Identifiers

PMID24887205
PMCPMC4049373
OpenAlexW2137499582

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.