Evidence map›Paper›PMID 21091652›Full record

ArticleBritish journal of pharmacology2011

Microarray analysis of nemorosone-induced cytotoxic effects on pancreatic cancer cells reveals activation of the unfolded protein response (UPR).

Frank Holtrup, Andrea Bauer, Kurt Fellenberg, Ralf A Hilger, Michael Wink, Jörg D Hoheisel

Open access · bronzeAbstract readValidation Study
In one paragraph

Article in British journal of pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 18% 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

18 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Review
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  10. Article
  11. Nemorosone and its emerging anti-neoplastic effects.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2013
    Article
  12. Chemosensitivity of conjunctival melanoma cell lines to target-specific chemotherapeutic agents.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2013
    Article
  13. Article
  14. Genomic analysis of pterostilbene predicts its antiproliferative effects against pancreatic cancer in vitro and in vivo.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2012
    Article
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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

6 authors at 4 institutions in 1 country.

Frank HoltrupFunctional Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg, Germany. f.holtrup@dkfz.de
Andrea Bauer
Kurt Fellenberg
Ralf A Hilger
Michael Wink
Jörg D Hoheisel
Heidelberg University · DEEssen University Hospital · DEGerman Cancer Research Center · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposePancreatic cancer is one of the leading cancer-related causes of death due to high chemo-resistance and fast metastasation. Nemorosone, a polycyclic polyprenylated acylphloroglucinol, has recently been identified as a promising anticancer agent. Here, we examine its growth-inhibitory effects on pancreatic cancer cells. Based on transcription profiling, a molecular mode of action is proposed. EXPERIMENTAL APPROACH: Nemorosone cytotoxicity was assessed by the resazurin proliferation assay on pancreatic cancer cells and fibroblasts. Apoptosis was determined by Annexin V/propidium iodide staining as well as cytochrome c and caspase activation assays. Staining with the voltage-dependent dye JC-1 and fluorescence microscopy were used to detect effects on mitochondrial membrane potential. Total RNA was isolated from treated cell lines and subjected to microarray analysis, subsequent pathway identification and modelling. Gene expression data were validated by quantitative polymerase chain reaction and siRNA-mediated gene knock-down. KEY

resultsNemorosone significantly inhibited cancer cell growth, induced cytochrome c release and subsequent caspase-dependent apoptosis, rapidly abolished mitochondrial membrane potential and elevated cytosolic calcium levels, while fibroblasts were largely unaffected. Expression profiling revealed 336 genes to be affected by nemorosone. A total of 75 genes were altered in all three cell lines, many of which were within the unfolded protein response (UPR) network. DNA damage inducible transcript 3 was identified as a key regulator in UPR-mediated cell death. CONCLUSIONS AND IMPLICATIONS: Nemorosone could be a lead compound for the development of novel anticancer drugs amplifying the already elevated UPR level in solid tumours, thus driving them into apoptosis. This study forms the basis for further investigations identifying nemorosone's direct molecular target(s).

Indexed as

Antineoplastic Agents, PhytogenicApoptosisBase SequenceBenzophenonesCalciumCaspasesCell CycleCell Line, TumorCell ProliferationCytochromes cDrug Screening Assays, AntitumorEndoplasmic ReticulumGene Expression ProfilingHumansMembrane Potential, MitochondrialOligonucleotide Array Sequence AnalysisAntineoplastic Agents, PhytogenicBenzophenonesCalciumCaspasesCytochromes cDDIT3 protein, humannemorosoneRNA, Small InterferingTranscription Factor CHOP

Identifiers

PMID21091652
PMCPMC3051378
OpenAlexW1600437736

What OpenQuestion holds

Textmetadata
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.