Evidence map›Paper›PMID 18501396›Full record

ArticleToxicology and applied pharmacology2008

Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent.

Samuel C McNeely, B Frazier Taylor, J Christopher States

Open access · greenAbstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 26% 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

16 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  7. Review
  8. Disruption of Mitotic Progression by Arsenic.Biological trace element research · 2015
    Review
  9. 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

3 authors at 1 institution in 1 country.

Samuel C McNeelyDepartment of Pharmacology and Toxicology, Center for Environmental Genomics and Integrative Biology, Center for Genetics and Molecular Medicine and Brown Cancer Center, University of Louisville, 570 S. Preston St. Suite 221, Louisville, KY 40202, USA.
B Frazier Taylor
J Christopher States
University of Louisville Hospital · US

Funding

UOFL ENVIRONMENTAL HEALTH SCIENCES TRAINING PROGRAMT32ES011564 · NIEHS · UNIVERSITY OF LOUISVILLE · PI David W Hein, John Pierce Wise · 2004 to 2026
$7.1M
Strategic Vision & Impact on Environmental HealthP30ES014443 · NIEHS · UNIVERSITY OF LOUISVILLE · PI DARLING, DOUGLAS S · 2007 to 2010
$4.4M
Arsenic Induced Miotic Arrest Associated ApoptosisR01ES011314 · NIEHS · UNIVERSITY OF LOUISVILLE · PI STATES, J CHRISTOPHER · 2003 to 2009
$1.4M
Arsenite inhibition of mitotic progressionF30ES013372 · NIEHS · UNIVERSITY OF LOUISVILLE · PI TAYLOR, BEN F · 2004 to 2008
$152k
NIEHS NIH HHS F30 ES013372NIEHS NIH HHS F30ES013372NIEHS NIH HHS P30 ES014443NIEHS NIH HHS P30ES014443NIEHS NIH HHS R01 ES011314NIEHS NIH HHS R01ES011314NIEHS NIH HHS T32 ES011564NIEHS NIH HHS T32ES011564
6 · The paper itself

Abstract

A375 human malignant melanoma cells undergo mitotic arrest-associated apoptosis when treated with pharmacological concentrations of sodium arsenite, a chemotherapeutic for acute promyelocytic leukemia. Our previous studies indicated that decreased arsenite sensitivity correlated with reduced mitotic spindle checkpoint function and reduced expression of the checkpoint protein BUBR1. In the current study, arsenite induced securin and cyclin B stabilization, BUBR1 phosphorylation, and spindle checkpoint activation. Arsenite also increased activating cyclin dependent kinase 1 (CDK1) Thr(161) phosphorylation but decreased inhibitory Tyr15 phosphorylation. Mitotic arrest resulted in apoptosis as indicated by colocalization of mitotic phospho-Histone H3 with active caspase 3. Apoptosis was associated with BCL-2 Ser70 phosphorylation. Inhibition of CDK1 with roscovitine in arsenite-treated mitotic cells inhibited spindle checkpoint maintenance as inferred from reduced BUBR1 phosphorylation, reduced cyclin B expression, and diminution of mitotic index. Roscovitine also reduced BCL-2 Ser70 phosphorylation and protected against apoptosis, suggesting mitotic arrest caused by hyperactivation of CDK1 directly or indirectly leads to BCL-2 phosphorylation and apoptosis. In addition, suppression of BUBR1 with siRNA prevented arsenite-induced mitotic arrest and apoptosis. These findings provide insight into the mechanism of arsenic's chemotherapeutic action and indicate a functional spindle checkpoint may be required for arsenic-sensitivity.

Indexed as

Antineoplastic AgentsAntineoplastic Agents, PhytogenicApoptosisArsenitesBlotting, WesternCDC2 Protein KinaseFluorescent Antibody TechniqueHumansMelanoma, ExperimentalMitosisNocodazolePaclitaxelProtein Serine-Threonine KinasesPurinesRNA, Small InterferingRoscovitineAntineoplastic AgentsAntineoplastic Agents, PhytogenicArsenitesBUB1 protein, humanBub1 spindle checkpoint proteinCDC2 Protein KinaseNocodazolePaclitaxelProtein Serine-Threonine KinasesPurinesRNA, Small InterferingRoscovitinesodium arseniteSodium Compounds

Identifiers

PMID18501396
PMCPMC2806883
OpenAlexW2046859044

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.