Evidence map›Paper›PMID 24906137›Full record

ArticleThe Journal of investigative dermatology2014

The epigenetic regulator I-BET151 induces BIM-dependent apoptosis and cell cycle arrest of human melanoma cells.

Stuart J Gallagher, Branka Mijatov, Dilini Gunatilake, Jessamy C Tiffen, Kavitha Gowrishankar, Lei Jin, Gulietta M Pupo, Carleen Cullinane, Rab K Prinjha, Nicholas Smithers and 3 more

Registry-linked trialOpen access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03655704 (Apabetalone for Pulmonary Arterial Hypertension), which is not on this map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.1field-weighted citation impact, top 5% 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.

NCT03655704 early_phase1completednot on this mapstarted 2019, after this paper: background citation

Apabetalone for Pulmonary Arterial Hypertension: a Pilot Study

TypeinterventionalSponsorSteeve ProvencherRan2019 to 2021Enrolled7ConditionsPulmonary Arterial HypertensionArmsApabetalone
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 63 citations in OpenAlex.

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  3. Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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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

13 authors at 4 institutions in 2 countries.

Stuart J GallagherMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.
Branka MijatovMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.
Dilini GunatilakeMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.
Jessamy C TiffenMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.
Kavitha GowrishankarMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.
Lei JinMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia.
Gulietta M PupoWestmead Institute for Cancer Research, The University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia.
Carleen CullinaneTranslational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Rab K PrinjhaEpinova Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
Nicholas SmithersEpinova Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK.
Grant A McArthurTranslational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Helen RizosWestmead Institute for Cancer Research, The University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia.
Peter HerseyMelanoma Research Group, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia; Melanoma Institute of Australia, North Sydney, New South Wales, Australia. Electronic address: peter.hersey@sydney.edu.au.
The University of Sydney · AUGlaxoSmithKline (United Kingdom) · GBPeter MacCallum Cancer Centre · AUMelanoma Institute Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic changes are widespread in melanoma and contribute to the pathogenic biology of this disease. In the present study, we show that I-BET151, which belongs to a new class of drugs that target the BET family of epigenetic "reader" proteins, inhibits melanoma growth in vivo and induced variable degrees of apoptosis in a panel of melanoma cells. Apoptosis was caspase dependent and associated with G1 cell cycle arrest. All melanoma cells tested had increased levels of the BH3 proapoptotic protein BIM, which appeared to be regulated by the BRD2 BET protein and to some extent by BRD3. In contrast, knockdown experiments indicated that inhibition of BRD4 was associated with decreased levels of BIM. Apoptosis was dependent on BIM in some but not all cell lines, indicating that other factors were determinants of apoptosis, such as downregulation of antiapoptotic proteins revealed in gene expression arrays. G1 cell cycle arrest appeared to be mediated by p21 and resulted from inhibition of the BRD4 protein. The activity of BET protein inhibitors appears independent of the BRAF and NRAS mutational status of melanoma, and further studies to assess their therapeutic role in melanoma are warranted.

Indexed as

Epigenesis, GeneticGene Expression Regulation, NeoplasticAnimalsApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11Bromodomain Containing ProteinsCaspasesCell Cycle CheckpointsCell Cycle ProteinsCell LineCell Line, TumorCell SurvivalCyclin-Dependent Kinase Inhibitor p21DNA Mutational AnalysisFemaleApoptosis Regulatory ProteinsBCL2L11 protein, humanBcl2l11 protein, mouseBcl-2-Like Protein 11BRAF protein, humanBRD4 protein, humanBromodomain Containing ProteinsCaspasesCDKN1A protein, humanCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p21GSK1210151AGTP PhosphohydrolasesHeterocyclic Compounds, 4 or More RingsMembrane ProteinsMonomeric GTP-Binding ProteinsNRAS protein, humanNras protein, mouseNuclear ProteinsProto-Oncogene ProteinsProto-Oncogene Proteins B-rafTranscription Factors

Identifiers

PMID24906137
OpenAlexW2079076045

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.