Evidence map›Paper›PMID 24040019›Full record

ArticlePloS one2013

Synergistic apoptosis of CML cells by buthionine sulfoximine and hydroxychavicol correlates with activation of AIF and GSH-ROS-JNK-ERK-iNOS pathway.

Avik Acharya Chowdhury, Jaydeep Chaudhuri, Nabendu Biswas, Anirban Manna, Saurav Chatterjee, Sanjit K Mahato, Utpal Chaudhuri, Parasuraman Jaisankar, Santu Bandyopadhyay

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.6field-weighted citation impact, top 12% 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

23 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Hydroxychavicol, a polyphenol fromJournal of Zhejiang University. Science. B · 2021
    Article
  7. Article
  8. Tanshinone I inhibited growth of human chronic myeloid leukemia cells via JNK/ERK mediated apoptotic pathways.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2021
    Article
  9. Article
  10. Article
  11. Apoptotic effects of hsian-tsao (Food science & nutrition · 2019
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Avik Acharya ChowdhuryDivision of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology (IICB), Kolkata, India.
Jaydeep Chaudhuri
Nabendu Biswas
Anirban Manna
Saurav Chatterjee
Sanjit K Mahato
Utpal Chaudhuri
Parasuraman Jaisankar
Santu Bandyopadhyay
Indian Institute of Chemical Biology · INCouncil of Scientific and Industrial Research · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHydroxychavicol (HCH), a constituent of Piper betle leaf has been reported to exert anti-leukemic activity through induction of reactive oxygen species (ROS). The aim of the study is to optimize the oxidative stress -induced chronic myeloid leukemic (CML) cell death by combining glutathione synthesis inhibitor, buthionine sulfoximine (BSO) with HCH and studying the underlying mechanism. MATERIALS AND

methodsAnti-proliferative activity of BSO and HCH alone or in combination against a number of leukemic (K562, KCL22, KU812, U937, Molt4), non-leukemic (A549, MIA-PaCa2, PC-3, HepG2) cancer cell lines and normal cell lines (NIH3T3, Vero) was measured by MTT assay. Apoptotic activity in CML cell line K562 was detected by flow cytometry (FCM) after staining with annexin V-FITC/propidium iodide (PI), detection of reduced mitochondrial membrane potential after staining with JC-1, cleavage of caspase- 3 and poly (ADP)-ribose polymerase proteins by western blot analysis and translocation of apoptosis inducing factor (AIF) by confocal microscopy. Intracellular reduced glutathione (GSH) was measured by colorimetric assay using GSH assay kit. 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) and 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) were used as probes to measure intracellular increase in ROS and nitric oxide (NO) levels respectively. Multiple techniques like siRNA transfection and pharmacological inhibition were used to understand the mechanisms of action.

resultsNon-apoptotic concentrations of BSO significantly potentiated HCH-induced apoptosis in K562 cells. BSO potentiated apoptosis-inducing activity of HCH in CML cells by caspase-dependent as well as caspase-independent but apoptosis inducing factor (AIF)-dependent manner. Enhanced depletion of intracellular GSH induced by combined treatment correlated with induction of ROS. Activation of ROS- dependent JNK played a crucial role in ERK1/2 activation which subsequently induced the expression of inducible nitric oxide synthase (iNOS). iNOS- mediated production of NO was identified as an effector molecule causing apoptosis of CML cells. CONCLUSION/SIGNIFICANCE: BSO synergizes with HCH in inducing apoptosis of CML cells through the GSH-ROS-JNK-ERK-iNOS pathway.

Indexed as

AnimalsApoptosisApoptosis Inducing FactorBlotting, WesternButhionine SulfoximineCell Line, TumorChlorocebus aethiopsDrug SynergismEugenolExtracellular Signal-Regulated MAP KinasesGlutathioneHep G2 CellsHumansJNK Mitogen-Activated Protein KinasesK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL Positive2-hydroxychavicolAIFM1 protein, humanApoptosis Inducing FactorButhionine SulfoximineEugenolExtracellular Signal-Regulated MAP KinasesGlutathioneJNK Mitogen-Activated Protein KinasesNitric OxideNitric Oxide Synthase Type IIReactive Oxygen Species

Identifiers

PMID24040019
PMCPMC3767640
OpenAlexW2009024313

What OpenQuestion holds

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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.