Evidence map›Paper›PMID 39397207›Full record

ArticleBreast cancer research and treatment2025

APX2009 sensitizes hypoxic breast cancer cells to doxorubicin by increasing its accumulation and caspase-3/7-mediated apoptosis.

Ísis Salviano Soares de Amorim, Daphne Pinheiro, Matheus da Silva Oliveira, Mariana Moreno de Sousa Rodrigues, Julia Silva José, Priscyanne Barreto Siqueira, Bruno Ricardo Barreto Pires, Adenilson de Souza da Fonseca, Andre Luiz Mencalha

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Article in Breast cancer research and treatment, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. 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

9 authors.

Ísis Salviano Soares de Amorim *Laboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0002-2762-1400
Daphne Pinheiro *Laboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0002-0986-971X
Matheus da Silva OliveiraLaboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0001-5261-3878
Mariana Moreno de Sousa RodriguesLaboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0003-0224-7288
Julia Silva JoséLaboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0009-0001-7673-3273
Priscyanne Barreto SiqueiraLaboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0003-2023-6048
Bruno Ricardo Barreto PiresLaboratório de Regulação E Expressão Gênica, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0002-0429-7871
Adenilson de Souza da FonsecaLaboratório de Biofotônica, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.ORCID http://orcid.org/0000-0002-4441-4008
Andre Luiz MencalhaLaboratório de Biologia Do Câncer, Instituto de Biologia Roberto Alcântara Gomes, Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. almencalha@yahoo.com.br.ORCID http://orcid.org/0000-0003-3229-8094

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico 302095/2022-5Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro E-26/200.318/2023
6 · The paper itself

Abstract

purposeThe association of targeted therapy with chemotherapy is encouraged to increase the treatment efficiency, especially in hypoxic triple-negative breast cancer. The APE1 redox activity has stood out as a potential tumor target. However, the effect of the association of the APE1 redox inhibitors with doxorubicin in hypoxia still needs to be evidenced. Therefore, our objective was to investigate the effect of the APX2009 (APE1 inhibitor) on the sensitization of breast cancer cells to doxorubicin in normoxia and hypoxia.

methodsThe WST-1 assay was used to evaluate cell viability after APX2009 and doxorubicin application under normoxia and hypoxia conditions in the MCF-7 and MDA-MB-231 cells. Apoptosis was analyzed by annexin assay and detection of caspases-3/7 activity by luminescence-based assay. The clinical association between APE1 inhibition signature and doxorubicin sensitivity was evaluated by bioinformatics analyses.

resultsMDA-MB-231 and MCF-7 cell lines were more sensitive to APX2009 in normoxia than in hypoxia. Co-treatment with APX2009 and doxorubicin in hypoxia further decreased the viability of triple-negative MDA-MB-231 cells than treatment alone, which was accompanied by doxorubicin intracellular accumulation, and increase of apoptotic cells percentage, and caspases-3/7 activity. Moderate association was found between APE1 inhibition signature and doxorubicin sensitivity in the hypoxic basal subtype.

conclusionThe findings suggest that APX2009 sensitizes the MDA-MB-231 cells to doxorubicin in hypoxia by doxorubicin intracellular accumulation and caspases-3/7-mediated apoptosis.

Indexed as

ApoptosisBreast NeoplasmsCaspase 3Caspase 7DNA-(Apurinic or Apyrimidinic Site) LyaseDoxorubicinAmidesAntibiotics, AntineoplasticCell HypoxiaCell Line, TumorCell SurvivalDrug Resistance, NeoplasmFemaleHumansMCF-7 CellsPhthalic AcidsAmidesAntibiotics, AntineoplasticAPEX1 protein, humanCASP3 protein, humanCASP7 protein, humanCaspase 3Caspase 7DNA-(Apurinic or Apyrimidinic Site) LyaseDoxorubicinPhthalic AcidsAPE1ApoptosisBreast cancerDoxorubicinHypoxia

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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.