Evidence map›Paper›PMID 24521712›Full record

ArticleCancer biology & therapy2014

Specific glycogen synthase kinase-3 inhibition reduces neuroendocrine markers and suppresses neuroblastoma cell growth.

Yvette M Carter, Selvi Kunnimalaiyaan, Herbert Chen, T Clark Gamblin, Muthusamy Kunnimalaiyaan

Open access · bronzeAbstract read
In one paragraph

Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 42 citations in OpenAlex.

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  17. Molecular Pathways: Revisiting Glycogen Synthase Kinase-3β as a Target for the Treatment of Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Yvette M CarterUniversity of Wisconsin Endocrine Surgery Laboratory; Madison, WI USA.
Selvi KunnimalaiyaanUniversity of Wisconsin Endocrine Surgery Laboratory; Madison, WI USA; Medical College of Wisconsin; Milwaukee, WI USA.
Herbert ChenUniversity of Wisconsin Endocrine Surgery Laboratory; Madison, WI USA.
T Clark GamblinMedical College of Wisconsin; Milwaukee, WI USA.
Muthusamy KunnimalaiyaanUniversity of Wisconsin Endocrine Surgery Laboratory; Madison, WI USA; Medical College of Wisconsin; Milwaukee, WI USA.
Madison Group (United States) · USMedical College of Wisconsin · USUniversity of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
GSK3-beta Signaling in Medullary Thyroid CancerR01CA121115 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CHEN, HERBERT · 2009 to 2013
$1.5M
UNSATURATED POLYOLEFINS AND HYDROCARBON CARCINOGENESISR01CA012115 · NCI · OHIO STATE UNIVERSITY · PI PAQUETTE, LEO A · 1985 to 1995
–
NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA121115NCI NIH HHS R01 CA12115-02S1
6 · The paper itself

Abstract

objectiveNeuroblastoma is a common neuroendocrine (NE) tumor that presents in early childhood, with a high incidence of malignancy and recurrence. The glycogen synthase kinase-3 (GSK-3) pathway is a potential therapeutic target, as this pathway has been shown to be crucial in the management of other NE tumors. However, it is not known which isoform is necessary for growth inhibition. In this study, we investigated the effect of the GSK-3 inhibitor AR-A014418 on the different GSK-3 isoforms in neuroblastoma.

methodsNGP and SH-5Y-SY cells were treated with 0-20 μM of AR-A014418 and cell viability was measured by MTT assay. Expression levels of NE markers CgA and ASCL1, GSK-3 isoforms, and apoptotic markers were analyzed by western blot.

resultsNeuroblastoma cells treated with AR-A014418 had a significant reduction in growth at all doses and time points (P<0.001). A reduction in growth was noted in cell lines on day 6, with 10 μM (NGP-53% vs. 0% and SH-5Y-SY-38% vs. 0%, P<0.001) treatment compared to control, corresponding with a noticeable reduction in tumor marker ASCL1 and CgA expression.

conclusionTreatment of neuroblastoma cell lines with AR-A014418 reduced the level of GSK-3α phosphorylation at Tyr279 compared to GSK-3β phosphorylation at Tyr216, and attenuated growth via the maintenance of apoptosis. This study supports further investigation to elucidate the mechanism(s) by which GSK-3α inhibition downregulates the expression of NE tumor markers and growth of neuroblastoma.

Indexed as

Antineoplastic AgentsApoptosisBasic Helix-Loop-Helix ProteinsBiomarkers, TumorBone Marrow NeoplasmsCell Line, TumorCell ProliferationChromogranin AGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansNeuroblastomaPhosphorylationThiazolesTyrosineUreaAntineoplastic AgentsASCL1 protein, humanBasic Helix-Loop-Helix ProteinsBiomarkers, TumorChromogranin AGlycogen Synthase Kinase 3glycogen synthase kinase 3 alphaGlycogen Synthase Kinase 3 betaGSK3B protein, humanN-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)ureaThiazolesTyrosineUreaapoptosisAR-A014418GSK3neuroblastoma

Identifiers

PMID24521712
PMCPMC4026073
OpenAlexW2048732666

What OpenQuestion holds

Textmetadata
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Registered trials

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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.