Evidence map›Paper›PMID 30410118›Full record

ArticleScientific reports2018

The Antiarrhythmic Drug, Dronedarone, Demonstrates Cytotoxic Effects in Breast Cancer Independent of Thyroid Hormone Receptor Alpha 1 (THRα1) Antagonism.

Mitchell J Elliott, Katarzyna J Jerzak, Jessica G Cockburn, Zhaleh Safikhani, William D Gwynne, John A Hassell, Anita Bane, Jennifer Silvester, Kelsie L Thu, Benjamin Haibe-Kains and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. 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
0.9field-weighted citation impact, top 21% 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, 15 citations in OpenAlex.

  1. Article
  2. Article
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  6. Review
  7. Targeting Ion Channels for Cancer Treatment: Current Progress and Future Challenges.Reviews of physiology, biochemistry and pharmacology · 2022
    Review
  8. 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

12 authors at 4 institutions in 1 country.

Mitchell J ElliottThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Katarzyna J JerzakSunnybrook Health Science Centre, Odette Cancer Centre, Toronto, Canada.
Jessica G CockburnMcMaster University, Hamilton, Canada.
Zhaleh SafikhaniThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.ORCID http://orcid.org/0000-0002-1429-1692
William D GwynneMcMaster University, Hamilton, Canada.
John A HassellMcMaster University, Hamilton, Canada.
Anita BaneMcMaster University, Hamilton, Canada.
Jennifer SilvesterThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Kelsie L ThuThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Benjamin Haibe-KainsThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
Tak W MakThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
David W CesconThe Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. dave.cescon@uhn.ca.
University Health Network · CAMcMaster University · CASunnybrook Health Science Centre · CAUniversity of Toronto · CA

Funding

CIHR
6 · The paper itself

Abstract

Previous research has suggested that thyroid hormone receptor alpha 1 (THRα1), a hormone responsive splice variant, may play a role in breast cancer progression. Whether THRα1 can be exploited for anti-cancer therapy is unknown. The antiproliferative and antitumor effects of dronedarone, an FDA-approved anti-arrhythmic drug which has been shown to antagonize THRα1, was evaluated in breast cancer cell lines in vitro and in vivo. The THRα1 splice variant and the entire receptor, THRα, were also independently targeted using siRNA to determine the effect of target knockdown in vitro. In our study, dronedarone demonstrates cytotoxic effects in vitro and in vivo in breast cancer cell lines at doses and concentrations that may be clinically relevant. However, knockdown of either THRα1 or THRα did not cause substantial anti-proliferative or cytotoxic effects in vitro, nor did it alter the sensitivity to dronedarone. Thus, we conclude that dronedarone's cytotoxic effect in breast cancer cell lines are independent of THRα or THRα1 antagonism. Further, the depletion of THRα or THRα1 does not affect cell viability or proliferation. Characterizing the mechanism of dronedarone's anti-tumor action may facilitate drug repurposing or the development of new anti-cancer agents.

Indexed as

AnimalsAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalDronedaroneDrug RepositioningFemaleHumansMiceRNA, Small InterferingThyroid Hormone Receptors alphaXenograft Model Antitumor AssaysAntineoplastic AgentsDronedaroneRNA, Small InterferingThyroid Hormone Receptors alpha

Identifiers

PMID30410118
PMCPMC6224430
OpenAlexW2898683666

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.