Evidence map›Paper›PMID 27894093›Full record

ArticleOncotarget2017

New use of an old drug: inhibition of breast cancer stem cells by benztropine mesylate.

Jihong Cui, Maija Hollmén, Lina Li, Yong Chen, Steven T Proulx, Daniel Reker, Gisbert Schneider, Michael Detmar

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 14% 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

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

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Drug Repurposing for Triple-Negative Breast Cancer.Journal of personalized medicine · 2020
    Review
  6. Article
  7. Review
  8. Article
  9. 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

8 authors at 1 institution in 1 country.

Jihong CuiInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Maija HollménInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Lina LiInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Yong ChenInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Steven T ProulxInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Daniel RekerInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Gisbert SchneiderInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
Michael DetmarInstitute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zürich, Zürich, Switzerland.
ETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells). 19 compounds were identified from screening. The chemically related molecules benztropine mesylate and deptropine citrate were selected for further validation and both potently inhibited sphere formation and self-renewal of BCSCs in vitro. Benztropine mesylate treatment decreased cell subpopulations with high ALDH activity and with a CD44+/CD24- phenotype. In vivo, benztropine mesylate inhibited tumor-initiating potential in a 4T1 mouse model. Functional studies indicated that benztropine mesylate inhibits functions of CSCs via the acetylcholine receptors, dopamine transporters/receptors, and/or histamine receptors. In summary, our findings identify benztropine mesylate as an inhibitor of BCSCs in vitro and in vivo. This study also provides a screening platform for identification of additional anti-CSC agents.

Indexed as

Drug RepositioningAnimalsAntineoplastic AgentsAntiparkinson AgentsBenztropineBiomarkersBreast NeoplasmsCell Line, TumorCell ProliferationCell Self RenewalCell SurvivalDisease Models, AnimalDrug Screening Assays, AntitumorFemaleHumansImmunophenotypingAntineoplastic AgentsAntiparkinson AgentsBenztropineBiomarkersSmall Molecule Librariesbenztropine mesylatebreast cancer stem cellscell-based phenotypic screeningNCI DTP-diversity set IIPrestwick library

Identifiers

PMID27894093
PMCPMC5352030
OpenAlexW2554274047

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.