Evidence map›Paper›PMID 37568682›Full record

ArticleCancers2023

The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells.

Keli Lima, Lívia Bassani Lins de Miranda, Anali Del Milagro Bernabe Garnique, Bruna Oliveira de Almeida, Mariane Cristina do Nascimento, Guilherme Augusto Sousa Alcântara, Glaucia Maria Machado-Santelli, Eduardo Magalhães Rego, João Agostinho Machado-Neto

Abstract read
In one paragraph

Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. ModulatingAging · 2024
    Article
  5. Article
  6. The role of autophagy in pancreatic diseases.Frontiers in pharmacology · 2024
    Review
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

9 authors.

Keli LimaLaboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo 01246-903, Brazil.ORCID 0000-0002-5498-7539
Lívia Bassani Lins de MirandaDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.ORCID 0000-0001-6635-0247
Anali Del Milagro Bernabe GarniqueDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.ORCID 0000-0001-6305-539X
Bruna Oliveira de AlmeidaDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
Mariane Cristina do NascimentoLaboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo 01246-903, Brazil.
Guilherme Augusto Sousa AlcântaraDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.
Glaucia Maria Machado-SantelliDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.ORCID 0000-0003-2046-9693
Eduardo Magalhães RegoLaboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Internal Medicine, Hematology Division, Faculdade de Medicina, University of São Paulo, São Paulo 01246-903, Brazil.
João Agostinho Machado-NetoDepartment of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-000, Brazil.ORCID 0000-0002-2937-8109

Funding

Coordenação de Aperfeicoamento de Pessoal de Nível Superior Finance Code 001São Paulo Research Foundation 2019/23864-7São Paulo Research Foundation 2019/25421-5São Paulo Research Foundation 2020/12842-0São Paulo Research Foundation 2021/11606-3São Paulo Research Foundation 2022/03316-8
6 · The paper itself

Abstract

Significant advances in understanding the molecular complexity of the development and progression of pancreatic cancer have been made, but this disease is still considered one of the most lethal human cancers and needs new therapeutic options. In the present study, the antineoplastic effects of AD80, a multikinase inhibitor, were investigated in models of pancreatic cancer. AD80 reduced cell viability and clonogenicity and induced polyploidy in pancreatic cancer cells. At the molecular level, AD80 reduced RPS6 and histone H3 phosphorylation and induced γH2AX and PARP1 cleavage. Additionally, the drug markedly decreased AURKA phosphorylation and expression. In PANC-1 cells, AD80 strongly induced autophagic flux (consumption of LC3B and SQSTM1/p62). AD80 modulated 32 out of 84 autophagy-related genes and was associated with vacuole organization, macroautophagy, response to starvation, cellular response to nitrogen levels, and cellular response to extracellular stimulus. In 3D pancreatic cancer models, AD80 also effectively reduced growth independent of anchorage and cell viability. In summary, AD80 induces mitotic aberrations, DNA damage, autophagy, and apoptosis in pancreatic cancer cells. Our exploratory study establishes novel targets underlying the antineoplastic activity of the drug and provides insights into the development of therapeutic strategies for this disease.

Indexed as

AD80aurora kinasesautophagymultikinase inhibitorpancreatic cancer

Identifiers

PMID37568682
PMCPMC10417629

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Registered trials

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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.