Evidence map›Paper›PMID 27764794›Full record

ArticleOncotarget2016

The BET bromodomain inhibitor exerts the most potent synergistic anticancer effects with quinone-containing compounds and anti-microtubule drugs.

Pei Y Liu, Nicholas Sokolowski, Su T Guo, Faraz Siddiqi, Bernard Atmadibrata, Thomas J Telfer, Yuting Sun, Lihong Zhang, Denise Yu, Joshua Mccarroll and 17 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

8 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. BET-ting on Nrf2: How Nrf2 Signaling can Influence the Therapeutic Activities of BET Protein Inhibitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018
    Review
  7. Article
  8. Review
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

27 authors at 9 institutions in 3 countries.

Pei Y LiuChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Nicholas SokolowskiChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Su T GuoSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Faraz SiddiqiChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Bernard AtmadibrataChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Thomas J TelferSchool of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, Sydney, Australia.
Yuting SunChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Lihong ZhangChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Denise YuChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Joshua MccarrollChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Bing LiuChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Rui H YangDepartment of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
Xiang Y GuoDepartment of Molecular Biology, Shanxi Cancer Hospital and Institute, Affiliated Hospital of Shanxi Medical University, Shanxi, China.
Andrew E TeeChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Ken ItohDepartment of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Jenny WangChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Maria KavallarisChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Michelle HaberChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Murray D NorrisChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Belamy B CheungChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Jennifer A ByrneChildren's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Westmead, Australia.
David S ZieglerChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Glenn M MarshallChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
Marcel E DingerGarvan Institute of Medical Research, Darlinghurst, Australia.
Rachel CoddSchool of Medical Sciences (Pharmacology) and Bosch Institute, The University of Sydney, Sydney, Australia.
Xu D ZhangSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Tao LiuChildren's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia.
UNSW Sydney · AUChildren's Cancer Institute Australia · AUUniversity of Newcastle Australia · AUUniversity of Sydney · AUChildren's Hospital at Westmead · AUHirosaki University · JPShanxi Medical University · CNSt Vincent's Clinic · AUSydney Children's Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BET bromodomain inhibitors are very promising novel anticancer agents, however, single therapy does not cause tumor regression in mice, suggesting the need for combination therapy. After screening a library of 2697 small molecule compounds, we found that two classes of compounds, the quinone-containing compounds such as nanaomycin and anti-microtubule drugs such as vincristine, exerted the best synergistic anticancer effects with the BET bromodomain inhibitor JQ1 in neuroblastoma cells. Mechanistically, the quinone-containing compound nanaomycin induced neuroblastoma cell death but also activated the Nrf2-antioxidant signaling pathway, and the BET bromodomain proteins BRD3 and BRD4 formed a protein complex with Nrf2. Treatment with JQ1 blocked the recruitment of Nrf2 to the antioxidant responsive elements at Nrf2 target gene promoters, and JQ1 exerted synergistic anticancer effects with nanaomycin by blocking the Nrf2-antioxidant signaling pathway. JQ1 and vincristine synergistically induced neuroblastoma cell cycle arrest at the G2/M phase, aberrant mitotic spindle assembly formation and apoptosis, but showed no effect on cell survival in normal non-malignant cells. Importantly, co-treatment with JQ1 and vincristine synergistically suppressed tumor progression in neuroblastoma-bearing mice. These results strongly suggest that patients treated with BET bromodomain inhibitors in clinical trials should be co-treated with vincristine.

Indexed as

AnimalsAntineoplastic AgentsAzepinesBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorCell ProliferationCell SurvivalDrug SynergismGene Expression Regulation, NeoplasticHumansMiceNaphthoquinonesNeuroblastomaNF-E2-Related Factor 2Nuclear ProteinsAntineoplastic AgentsAzepinesBRD3 protein, humanBRD4 protein, humanBromodomain Containing ProteinsCell Cycle Proteins(+)-JQ1 compoundNaphthoquinonesNFE2L2 protein, humanNF-E2-Related Factor 2Nuclear ProteinsRNA-Binding ProteinsSmall Molecule LibrariesTranscription FactorsTriazolesTubulin ModulatorsVincristineJQ1nanaomycinneuroblastomaquinone-containing compoundsvincristine

Identifiers

PMID27764794
PMCPMC5346709
OpenAlexW2531661710

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.