Evidence map›Paper›PMID 24355564›Full record

ArticleBiochemical pharmacology2014

(R,R')-4'-methoxy-1-naphthylfenoterol targets GPR55-mediated ligand internalization and impairs cancer cell motility.

Rajib K Paul, Artur Wnorowski, Isabel Gonzalez-Mariscal, Surendra K Nayak, Karolina Pajak, Ruin Moaddel, Fred E Indig, Michel Bernier, Irving W Wainer

Abstract read
In one paragraph

Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Novel fenoterol derivatives as suppressors of ERK1/2 phosphorylation in melanoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026
    Article
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  5. Review
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  10. Concurrent activation of βCellular signalling · 2017
    Article
  11. Frontiers in pharmacology · 2017
    Article
  12. Article
  13. Article
  14. 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 at 2 institutions in 1 country.

Rajib K PaulLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA. Electronic address: paulrk@mail.nih.gov.
Artur WnorowskiLaboratory of Medicinal Chemistry and Neuroengineering, Department of Chemistry, Medical University of Lublin, 20-093 Lublin, Poland. Electronic address: artur.wnorowski@gmail.com.
Isabel Gonzalez-MariscalLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA. Electronic address: isabel.gonzalezmariscal@nih.gov.
Surendra K NayakSRI International (S.K.N.), Harrisonburg, VA 22802, USA. Electronic address: surendra.nayak@sri.com.
Karolina PajakLaboratory of Medicinal Chemistry and Neuroengineering, Department of Chemistry, Medical University of Lublin, 20-093 Lublin, Poland. Electronic address: karolina.pajak@umlub.pl.
Ruin MoaddelLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA. Electronic address: moaddelru@grc.nia.nih.gov.
Fred E IndigLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA. Electronic address: indigfr@grc.nia.nih.gov.
Michel BernierLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA. Electronic address: bernierm@mail.nih.gov.
Irving W WainerLaboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health (NIH), Baltimore, MD 21224, USA. Electronic address: wainerir@grc.nia.nih.gov.
National Institutes of Health · USSRI International · US

Funding

Disease Status Drug Metabolism and New Drug Discovery ZIAAG000297 · NIA · NATIONAL INSTITUTE ON AGING · PI EGAN, JOSEPHINE · 2009 to 2025
$38.2M
NIA/RRB Confocal Imaging FacilityZICAG000615 · NIA · NATIONAL INSTITUTE ON AGING · PI INDIG, FRED · 2009 to 2025
$17.9M
Intramural NIH HHS ZIA AG000297
6 · The paper itself

Abstract

(R,R')-4'-Methoxy-1-naphthylfenoterol (MNF) promotes growth inhibition and apoptosis of human HepG2 hepatocarcinoma cells via cannabinoid receptor (CBR) activation. The synthetic CB1R inverse agonist, AM251, has been shown to block the anti-mitogenic effect of MNF in these cells; however, AM251 is also an agonist of the recently deorphanized, lipid-sensing receptor, GPR55, whose upregulation contributes to carcinogenesis. Here, we investigated the role of MNF in GPR55 signaling in human HepG2 and PANC-1 cancer cell lines in culture by focusing first on internalization of the fluorescent ligand Tocrifluor 1117 (T1117). Initial results indicated that cell pretreatment with GPR55 agonists, including the atypical cannabinoid O-1602 and l-α-lysophosphatidylinositol, dose-dependently reduced the rate of cellular T1117 uptake, a process that was sensitive to MNF inhibition. GPR55 internalization and signaling mediated by O-1602 was blocked by MNF in GPR55-expressing HEK293 cells. Pretreatment of HepG2 and PANC-1 cells with MNF significantly abrogated the induction of ERK1/2 phosphorylation in response to AM251 and O-1602. Moreover, MNF exerted a coordinated negative regulation of AM251 and O-1602 inducible processes, including changes in cellular morphology and cell migration using scratch wound healing assay. This study shows for the first time that MNF impairs GPR55-mediated signaling and, therefore, may have therapeutic potential in the management of cancer.

Indexed as

Drug Inverse AgonismCell MovementEndocytosisFenoterolHEK293 CellsHep G2 CellsHumansLigandsMolecular Targeted TherapyNeoplasmsPiperidinesPyrazolesReceptor, Cannabinoid, CB1Receptors, CannabinoidReceptors, G-Protein-CoupledAM 251FenoterolGPR55 protein, humanLigandsPiperidinesPyrazolesReceptor, Cannabinoid, CB1Receptors, CannabinoidReceptors, G-Protein-CoupledCell motilityCellular morphologyGPR55G-protein coupled receptorLigand internalization

Identifiers

PMID24355564
PMCPMC3935314
OpenAlexW1994615999

What OpenQuestion holds

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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.