Evidence map›Paper›PMID 24959746›Full record

ArticlePloS one2014

Constitutive androstane receptor ligands modulate the anti-tumor efficacy of paclitaxel in non-small cell lung cancer cells.

Heidge Fukumasu, Arina L Rochetti, Pedro R L Pires, Edson R Silva, Ligia G Mesquita, Ricardo F Strefezzi, Daniel D De Carvalho, Maria L Dagli

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Small-molecule modulators of PXR and CAR.Biochimica et biophysica acta · 2016
    Review
  8. Small-molecule modulators of the constitutive androstane receptor.Expert opinion on drug metabolism & toxicology · 2015
    Review
  9. Expression of NR1I3 in mouse lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2015
    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

8 authors at 2 institutions in 2 countries.

Heidge FukumasuLaboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil.
Arina L RochettiLaboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil.
Pedro R L PiresLaboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil.
Edson R SilvaLaboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil.
Ligia G MesquitaLaboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil.
Ricardo F StrefezziLaboratory of Comparative and Translational Oncology, Department of Veterinary Medicine, School of Animal Science and Food Engineering, University of São Paulo, Pirassununga, Brazil.
Daniel D De CarvalhoCampbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Maria L DagliLaboratory of Experimental and Comparative Oncology, Department of Pathology, School of Veterinary Medicine and Animal Science of the University of São Paulo, Sao Paulo, Brazil.
Universidade de São Paulo · BRUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLung tumors are the leading cause of cancer deaths worldwide and paclitaxel has proven to be useful for patients with lung cancer, however, acquired resistance is a major problem. To overcome this problem, one promising option is the use of Constitutive Androstane Receptor (CAR) ligands in combination with chemotherapeutics against cancer cells. Therefore, we wish to elucidate the effects of CAR ligands on the antineoplastic efficacy of paclitaxel in lung cancer cells. METHODOLOGY/PRINCIPAL

findingsOur results from cell viability assays exposing CAR agonist or inverse-agonist to mouse and human lung cancer cells modulated the antineoplastic effect of paclitaxel. The CAR agonists increased the effect of Paclitaxel in 6 of 7 lung cancer cell lines, whereas the inverse-agonist had no effect on paclitaxel cytotoxicity. Interestingly, the mCAR agonist TCPOBOP enhanced the expression of two tumor suppressor genes, namely WT1 and MGMT, which were additively enhanced in cells treated with CAR agonist in combination with paclitaxel. Also, in silico analysis showed that both paclitaxel and CAR agonist TCPOBOP docked into the mCAR structure but not the inverse agonist androstenol. Paclitaxel per se increases the expression of CAR in cancer cells. At last, we analyzed the expression of CAR in two public independent studies from The Cancer Genome Atlas (TCGA) of Non Small Cell Lung Cancer (NSCLC). CAR is expressed in variable levels in NSCLC samples and no association with overall survival was noted. CONCLUSIONS/SIGNIFICANCE: Taken together, our results demonstrated that CAR agonists modulate the antineoplastic efficacy of paclitaxel in mouse and human cancer cell lines. This effect was probably related by the enhanced expression of two tumor suppressor genes, viz. WT1 and MGMT. Most of NSCLC cases present CAR gene expression turning it possible to speculate the use of CAR modulation by ligands along with Paclitaxel in NSCLC therapy.

Indexed as

AndrostenolsAnimalsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCell Line, TumorConstitutive Androstane ReceptorDNA Modification MethylasesDrug SynergismGene Expression Regulation, NeoplasticHumansLung NeoplasmsMiceOximesPaclitaxelPyridinesReceptors, Cytoplasmic and Nuclear1,4-bis(2-(3,5-dichloropyridyloxy))benzene6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oximeAndrostenolsAntineoplastic AgentsConstitutive Androstane ReceptorDNA Modification MethylasesOximesPaclitaxelPyridinesReceptors, Cytoplasmic and NuclearThiazolesWT1 Proteins

Identifiers

PMID24959746
PMCPMC4069004
OpenAlexW1993310369

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.