Evidence map›Paper›PMID 26298773›Full record

ArticleOncotarget2015

Tonantzitlolone cytotoxicity toward renal cancer cells is PKCθ- and HSF1-dependent.

Carole Sourbier, Bradley T Scroggins, Philip Z Mannes, Pei-Jyun Liao, Karsten Siems, Dietmar Wolf, John A Beutler, W Marston Linehan, Leonard Neckers

Abstract read
In one paragraph

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. NaScientific reports · 2017
    Article
  11. Englerins: A Comprehensive Review.Journal of natural products · 2017
    Review
  12. Synthesis of a stable and orally bioavailable englerin analogue.Bioorganic & medicinal chemistry letters · 2016
    Article
  13. Article
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

9 authors.

Carole SourbierUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Bradley T ScrogginsRadiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Philip Z MannesUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Pei-Jyun LiaoUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Karsten SiemsAnalytiCon Discovery GmbH, D-14473 Potsdam, Germany.
Dietmar WolfAnalytiCon Discovery GmbH, D-14473 Potsdam, Germany.
John A BeutlerMolecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
W Marston LinehanUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Leonard NeckersUrologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

Funding

Clinical Studies of the Molecular Genetic Basis of Kidney CancerZIABC011028 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LINEHAN, WILLIAM MARSTON · 2009 to 2025
$17.9M
Role of fumarate hydratase loss in development of HLRCC hereditary kidney cancerZIABC010683 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NECKERS, LEONARD · 2009 to 2024
$8.6M
Development of Natural Product Leads as Anticancer TherapeuticsZIABC011470 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BEUTLER, JOHN · 2012 to 2025
$7.8M
Role of FH loss in development of HLRCC heriditary kidney cancerZ01BC010683 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NECKERS, LEONARD · 2005 to 2008
$864k
Intramural NIH HHSNCI NIH HHS Z01BC010683-03PHS HHS 1ZIABC011038-07
6 · The paper itself

Abstract

Elucidating the targets and mechanism of action of natural products is strategically important prior to drug development and assessment of potential clinical applications. In this report, we elucidated the main targets and mechanism of action of the natural product tonantzitlolone (TZL) in clear cell renal cell carcinoma (CCRCC). We identified TZL as a dual PKCα and PKCθ activator in vitro, although in CCRCC cells its activity was mostly PKCθ-dependent. Through activation of PKCθ, TZL induced an insulin resistant phenotype by inhibiting IRS1 and the PI3K/Akt pathway. Simultaneously, TZL activated the heat shock factor 1 (HSF1) transcription factor driving glucose dependency. Thus, similar to the selective PKCθ activator englerin A, TZL induces a metabolic catastrophe in CCRCC, starving cells of glucose while simultaneously increasing their glycolytic dependency.

Indexed as

Antineoplastic AgentsCarcinoma, Renal CellCell Line, TumorCell SurvivalDiterpenesDNA-Binding ProteinsDose-Response Relationship, DrugEnzyme ActivationGlucoseHeat Shock Transcription FactorsHEK293 CellsHumansImmunoblottingIsoenzymesKidney NeoplasmsMacrocyclic CompoundsAntineoplastic AgentsDiterpenesDNA-Binding Proteinsenglerin AGlucoseHeat Shock Transcription FactorsHSF1 protein, humanIsoenzymesMacrocyclic CompoundsPRKCQ protein, humanProtein Kinase CProtein Kinase C-thetaSesquiterpenes, GuaianetonantzitloloneTranscription Factorsbryostatinenglerin APKCθRCCrenal tumors

Identifiers

PMID26298773
PMCPMC4745775

What OpenQuestion holds

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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.