Evidence map›Paper›PMID 34895240›Full record

ArticleBMC biology2021

Nanoscale characterization of drug-induced microtubule filament dysfunction using super-resolution microscopy.

Ashley M Rozario, Sam Duwé, Cade Elliott, Riley B Hargreaves, Gregory W Moseley, Peter Dedecker, Donna R Whelan, Toby D M Bell

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

Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

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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 5 institutions in 2 countries.

Ashley M RozarioSchool of Chemistry, Monash University, Clayton, 3800, Australia.
Sam DuwéBiomedical Research Institute, Hasselt University, 3590, Diepenbeek, Belgium.
Cade ElliottSchool of Chemistry, Monash University, Clayton, 3800, Australia.
Riley B HargreavesSchool of Chemistry, Monash University, Clayton, 3800, Australia.
Gregory W MoseleyDepartment of Microbiology, Monash Biomedicine Discovery Institute, Clayton, 3800, Australia.
Peter DedeckerDepartment of Chemistry, KU Leuven, 3001, Leuven, Belgium.
Donna R WhelanLa Trobe Institute for Molecular Science, La Trobe University, Bendigo, 3552, Australia. d.whelan@latrobe.edu.au.
Toby D M BellSchool of Chemistry, Monash University, Clayton, 3800, Australia. toby.bell@monash.edu.ORCID 0000-0002-4570-5595
Monash University · AUAustralian Regenerative Medicine Institute · AUHasselt University · BEKU Leuven · BELa Trobe University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe integrity of microtubule filament networks is essential for the roles in diverse cellular functions, and disruption of its structure or dynamics has been explored as a therapeutic approach to tackle diseases such as cancer. Microtubule-interacting drugs, sometimes referred to as antimitotics, are used in cancer therapy to target and disrupt microtubules. However, due to associated side effects on healthy cells, there is a need to develop safer drug regimens that still retain clinical efficacy. Currently, many questions remain open regarding the extent of effects on cellular physiology of microtubule-interacting drugs at clinically relevant and low doses. Here, we use super-resolution microscopies (single-molecule localization and optical fluctuation based) to reveal the initial microtubule dysfunctions caused by nanomolar concentrations of colcemid.

resultsWe identify previously undetected microtubule (MT) damage caused by clinically relevant doses of colcemid. Short exposure to 30-80 nM colcemid results in aberrant microtubule curvature, with a trend of increased curvature associated to increased doses, and curvatures greater than 2 rad/μm, a value associated with MT breakage. Microtubule fragmentation was detected upon treatment with ≥ 100 nM colcemid. Remarkably, lower doses (< 20 nM after 5 h) led to subtle but significant microtubule architecture remodelling characterized by increased curvature and suppression of microtubule dynamics.

conclusionsOur results support the emerging hypothesis that microtubule-interacting drugs induce non-mitotic effects in cells, and establish a multi-modal imaging assay for detecting and measuring nanoscale microtubule dysfunction. The sub-diffraction visualization of these less severe precursor perturbations compared to the established antimitotic effects of microtubule-interacting drugs offers potential for improved understanding and design of anticancer agents.

Indexed as

CytoskeletonMicrotubulesDemecolcineMicroscopy, FluorescenceDemecolcineAntimitoticColcemiddSTORMFilament curvatureLive cell imagingMicrotubulesSOFISuper-resolution

Identifiers

PMID34895240
PMCPMC8665533
OpenAlexW4200367532

What OpenQuestion holds

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LicenceCC BY
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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.