Evidence map›Paper›PMID 36871041›Full record

ArticleBritish journal of cancer2023

Azithromycin, a potent autophagy inhibitor for cancer therapy, perturbs cytoskeletal protein dynamics.

Naoharu Takano, Masaki Hiramoto, Yumiko Yamada, Hiroko Kokuba, Mayumi Tokuhisa, Hirotsugu Hino, Keisuke Miyazawa

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

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  14. ALDHCells · 2024
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  18. Oncology letters · 2024
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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

7 authors at 1 institution in 1 country.

Naoharu TakanoDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan. ntakano@tokyo-med.ac.jp.ORCID http://orcid.org/0000-0003-3364-2731
Masaki HiramotoDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.ORCID http://orcid.org/0000-0002-1076-6515
Yumiko YamadaDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Hiroko KokubaLaboratory of Electron Microscopy, Tokyo Medical University, Tokyo, Japan.
Mayumi TokuhisaDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Hirotsugu HinoDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan.
Keisuke MiyazawaDepartment of Biochemistry, Tokyo Medical University, Tokyo, Japan. miyazawa@tokyo-med.ac.jp.ORCID http://orcid.org/0000-0002-8435-1304
Tokyo Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutophagy plays an important role in tumour cell growth and survival and also promotes resistance to chemotherapy. Hence, autophagy has been targeted for cancer therapy. We previously reported that macrolide antibiotics including azithromycin (AZM) inhibit autophagy in various types of cancer cells in vitro. However, the underlying molecular mechanism for autophagy inhibition remains unclear. Here, we aimed to identify the molecular target of AZM for inhibiting autophagy.

methodsWe identified the AZM-binding proteins using AZM-conjugated magnetic nanobeads for high-throughput affinity purification. Autophagy inhibitory mechanism of AZM was analysed by confocal microscopic and transmission electron microscopic observation. The anti-tumour effect with autophagy inhibition by oral AZM administration was assessed in the xenografted mice model.

resultsWe elucidated that keratin-18 (KRT18) and α/β-tubulin specifically bind to AZM. Treatment of the cells with AZM disrupts intracellular KRT18 dynamics, and KRT18 knockdown resulted in autophagy inhibition. Additionally, AZM treatment suppresses intracellular lysosomal trafficking along the microtubules for blocking autophagic flux. Oral AZM administration suppressed tumour growth while inhibiting autophagy in tumour tissue.

conclusionsAs drug-repurposing, our results indicate that AZM is a potent autophagy inhibitor for cancer treatment, which acts by directly interacting with cytoskeletal proteins and perturbing their dynamics.

Indexed as

AzithromycinNeoplasmsAnimalsAnti-Bacterial AgentsAutophagyCytoskeletal ProteinsDisease Models, AnimalMacrolidesMiceAnti-Bacterial AgentsAzithromycinCytoskeletal ProteinsMacrolides

Identifiers

PMID36871041
PMCPMC10147625
OpenAlexW4323047247

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.