Evidence map›Paper›PMID 27324222›Full record

ArticleProstate cancer and prostatic diseases2016

The cannabinoid WIN 55,212-2 prevents neuroendocrine differentiation of LNCaP prostate cancer cells.

C Morell, A Bort, D Vara, A Ramos-Torres, N Rodríguez-Henche, I Díaz-Laviada

Open access · hybridAbstract read
In one paragraph

Article in Prostate cancer and prostatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Cannabinoids and Prostate Cancer: A Systematic Review of Animal Studies.International journal of molecular sciences · 2020
    Pooled it
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  13. Cannabinoids in the landscape of cancer.Journal of cancer research and clinical oncology · 2021
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  19. The Endocannabinoid System: A Target for Cancer Treatment.International journal of molecular sciences · 2020
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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 2 institutions in 2 countries.

C MorellDepartment of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Madrid, Spain.
A BortDepartment of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Madrid, Spain.
D VaraDivision of Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
A Ramos-TorresDepartment of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Madrid, Spain.
N Rodríguez-HencheDepartment of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Madrid, Spain.
I Díaz-LaviadaDepartment of System Biology, Biochemistry and Molecular Biology Unit, School of Medicine, Alcala University, Madrid, Spain.
Universidad de Alcalá · ESUniversity of Dundee · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeuroendocrine (NE) differentiation represents a common feature of prostate cancer and is associated with accelerated disease progression and poor clinical outcome. Nowadays, there is no treatment for this aggressive form of prostate cancer. The aim of this study was to determine the influence of the cannabinoid WIN 55,212-2 (WIN, a non-selective cannabinoid CB1 and CB2 receptor agonist) on the NE differentiation of prostate cancer cells.

methodsNE differentiation of prostate cancer LNCaP cells was induced by serum deprivation or by incubation with interleukin-6, for 6 days. Levels of NE markers and signaling proteins were determined by western blotting. Levels of cannabinoid receptors were determined by quantitative PCR. The involvement of signaling cascades was investigated by pharmacological inhibition and small interfering RNA.

resultsThe differentiated LNCaP cells exhibited neurite outgrowth, and increased the expression of the typical NE markers neuron-specific enolase and βIII tubulin (βIII Tub). Treatment with 3 μM WIN inhibited NK differentiation of LNCaP cells. The cannabinoid WIN downregulated the PI3K/Akt/mTOR signaling pathway, resulting in NE differentiation inhibition. In addition, an activation of AMP-activated protein kinase (AMPK) was observed in WIN-treated cells, which correlated with a decrease in the NE markers expression. Our results also show that during NE differentiation the expression of cannabinoid receptors CB1 and CB2 dramatically decreases.

conclusionsTaken together, we demonstrate that PI3K/Akt/AMPK might be an important axis modulating NE differentiation of prostate cancer that is blocked by the cannabinoid WIN, pointing to a therapeutic potential of cannabinoids against NE prostate cancer.

Indexed as

AMP-Activated Protein KinasesAnimalsBenzoxazinesBiomarkersCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalGene ExpressionHumansMaleMiceModels, BiologicalMorpholinesNaphthalenesNeuroendocrine TumorsPhosphatidylinositol 3-Kinases(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanoneAMP-Activated Protein KinasesBenzoxazinesBiomarkersMorpholinesNaphthalenesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2TOR Serine-Threonine Kinases

Identifiers

PMID27324222
PMCPMC5411672
OpenAlexW2466350629

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.