Evidence map›Paper›PMID 29751783›Full record

ArticleBMC cancer2018

Antiproliferative and apoptotic effect of LY2090314, a GSK-3 inhibitor, in neuroblastoma in vitro.

Selvi Kunnimalaiyaan, Victoriana K Schwartz, Iris Alao Jackson, T Clark Gamblin, Muthusamy Kunnimalaiyaan

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.7field-weighted citation impact, top 7% 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

31 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. The cross-talk between GSK-3β, RKIP, and PTEN as potential targets for therapeutic implications in cancer: a comprehensive insight.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026
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  17. Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021
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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

5 authors at 1 institution in 1 country.

Selvi KunnimalaiyaanDivision of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, C4763, Translational and Biomedical Research Center, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Victoriana K SchwartzDivision of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, C4763, Translational and Biomedical Research Center, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Iris Alao JacksonDivision of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, C4763, Translational and Biomedical Research Center, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
T Clark GamblinDivision of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, C4763, Translational and Biomedical Research Center, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Muthusamy KunnimalaiyaanDivision of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, C4763, Translational and Biomedical Research Center, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA. mkunnima@mcw.edu.ORCID http://orcid.org/0000-0003-3712-7497
Medical College of Wisconsin · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% of high-risk NB will have relapse and therefore long-term event free survival is very minimal. We have reported that targeting glycogen synthase kinase-3 (GSK-3) may be a potential strategy to treat NB. Consequently, investigating LY2090314, a clinically relevant GSK-3 inhibitor, on NB cellular proliferation and may be beneficial for NB treatment.

methodsThe effect of LY2090314 was compared with a previously studied GSK-3 inhibitor, Tideglusib. Colorimetric, clonogenic, and live-cell image confluency assays were used to study the proliferative effect of LY2090314 on NB cell lines (NGP, SK-N-AS, and SH-SY-5Y). Western blotting and caspase glo assay were performed to determine the mechanistic function of LY2090314 in NB cell lines.

resultsLY2090314 treatment exhibited significant growth reduction starting at a 20 nM concentration in NGP, SK-N-AS, and SH-SY-5Y cells. Western blot analysis indicated that growth suppression was due to apoptosis as evidenced by an increase in pro-apoptotic markers cleaved PARP and cleaved caspase-3 and a reduction in the anti-apoptotic protein, survivin. Further, treatment significantly reduced the level of cyclin D1, a key regulatory protein of the cell cycle and apoptosis. Functionally, this was confirmed by an increase in caspase activity. LY2090314 treatment reduced the expression levels of phosphorylated GSK-3 proteins and increased the stability of β-catenin in these cells.

conclusionsLY2090314 effectively reduces growth of both human MYCN amplified and non-amplified NB cell lines in vitro. To our knowledge, this is the first study to look at the effect of LY2090314 in NB cell lines. These results indicate that GSK-3 may be a therapeutic target for NB and provide rationale for further preclinical analysis using LY2090314.

Indexed as

Antineoplastic AgentsApoptosisCell Line, TumorCell ProliferationDrug Screening Assays, AntitumorGlycogen Synthase Kinase 3Heterocyclic Compounds, 3-RingHumansMaleimidesNeuroblastomaN-Myc Proto-Oncogene ProteinPhosphorylation3-(9-fluoro-2-(piperidin-1-ylcarbonyl)-1,2,3,4-tetrahydro(1,4)diazepino(6,7,1-hi)indol-7-yl)-4-imidazo(1,2-a)pyridin-3-yl-1H-pyrrole-2,5-dioneAntineoplastic AgentsGlycogen Synthase Kinase 3Heterocyclic Compounds, 3-RingMaleimidesMYCN protein, humanN-Myc Proto-Oncogene ProteinApoptosisGSK-3 alphaGSK-3 betaGSK-3 inhibitorNeuroblastoma

Identifiers

PMID29751783
PMCPMC5948712
OpenAlexW2805077659

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.