Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin

Elevated expression levels of the apurinic/apyrimidinic endonuclease 1 (APE1) have been correlated with the more aggressive phenotypes and poor prognosis of non-small cell lung cancer (NSCLC). This study aimed to assess the impact of the inhibition of the redox function of APE1 with E3330 either alo...

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Autores: Manguinhas, Rita, Fernandes, Ana S.|||0000-0001-6350-0641, Costa, João G.|||0000-0002-5604-6142, Saraiva, Nuno|||0000-0003-1333-9137, Camões, Sérgio P.|||0000-0003-0355-5338, Gil, Nuno|||0000-0002-6567-8379, Rosell, Rafael|||0000-0003-0817-3400, Castro, Matilde, Miranda, Joana P.|||0000-0002-7804-4068, Oliveira, Nuno G.
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252714
Acceso en línea:https://ddd.uab.cat/record/252714
https://dx.doi.org/urn:doi:10.3390/antiox9060550
Access Level:acceso abierto
Palabra clave:Non-small cell lung cancer
Cisplatin
Apurinic/apyrimidinic endonuclease 1
E3330
Cytotoxicity
Apoptosis
Migration
Invasion
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spelling Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to CisplatinIncreased Cytotoxicity and Impairment of Cell Migration and InvasionManguinhas, RitaFernandes, Ana S.|||0000-0001-6350-0641Costa, João G.|||0000-0002-5604-6142Saraiva, Nuno|||0000-0003-1333-9137Camões, Sérgio P.|||0000-0003-0355-5338Gil, Nuno|||0000-0002-6567-8379Rosell, Rafael|||0000-0003-0817-3400Castro, MatildeMiranda, Joana P.|||0000-0002-7804-4068Oliveira, Nuno G.Non-small cell lung cancerCisplatinApurinic/apyrimidinic endonuclease 1E3330CytotoxicityApoptosisMigrationInvasionElevated expression levels of the apurinic/apyrimidinic endonuclease 1 (APE1) have been correlated with the more aggressive phenotypes and poor prognosis of non-small cell lung cancer (NSCLC). This study aimed to assess the impact of the inhibition of the redox function of APE1 with E3330 either alone or in combination with cisplatin in NSCLC cells. For this purpose, complementary endpoints focusing on cell viability, apoptosis, cell cycle distribution, and migration/invasion were studied. Cisplatin decreased the viability of H1975 cells in a time- and concentration-dependent manner, with IC values of 9.6 µM for crystal violet assay and 15.9 µM for 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. E3330 was clearly cytotoxic for concentrations above 30 µM. The co-incubation of E3330 and cisplatin significantly decreased cell viability compared to cisplatin alone. Regarding cell cycle distribution, cisplatin led to an increase in sub-G1, whereas the co-treatment with E3330 did not change this profile, which was then confirmed in terms of % apoptotic cells. In addition, the combination of E3330 and cisplatin at low concentrations decreased collective and chemotactic migration, and also chemoinvasion, by reducing these capabilities up to 20%. Overall, these results point to E3330 as a promising compound to boost cisplatin therapy that warrants further investigation in NSCLC. 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/252714https://dx.doi.org/urn:doi:10.3390/antiox9060550reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaIngléseng"la Caixa" Foundation https://doi.org/10.13039/100010434 PROYE18012ROSEopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2527142026-06-06T12:50:31Z
dc.title.none.fl_str_mv Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
Increased Cytotoxicity and Impairment of Cell Migration and Invasion
title Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
spellingShingle Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
Manguinhas, Rita
Non-small cell lung cancer
Cisplatin
Apurinic/apyrimidinic endonuclease 1
E3330
Cytotoxicity
Apoptosis
Migration
Invasion
title_short Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
title_full Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
title_fullStr Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
title_full_unstemmed Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
title_sort Impact of the APE1 Redox Function Inhibitor E3330 in Non-Small Cell Lung Cancer Cells Exposed to Cisplatin
dc.creator.none.fl_str_mv Manguinhas, Rita
Fernandes, Ana S.|||0000-0001-6350-0641
Costa, João G.|||0000-0002-5604-6142
Saraiva, Nuno|||0000-0003-1333-9137
Camões, Sérgio P.|||0000-0003-0355-5338
Gil, Nuno|||0000-0002-6567-8379
Rosell, Rafael|||0000-0003-0817-3400
Castro, Matilde
Miranda, Joana P.|||0000-0002-7804-4068
Oliveira, Nuno G.
author Manguinhas, Rita
author_facet Manguinhas, Rita
Fernandes, Ana S.|||0000-0001-6350-0641
Costa, João G.|||0000-0002-5604-6142
Saraiva, Nuno|||0000-0003-1333-9137
Camões, Sérgio P.|||0000-0003-0355-5338
Gil, Nuno|||0000-0002-6567-8379
Rosell, Rafael|||0000-0003-0817-3400
Castro, Matilde
Miranda, Joana P.|||0000-0002-7804-4068
Oliveira, Nuno G.
author_role author
author2 Fernandes, Ana S.|||0000-0001-6350-0641
Costa, João G.|||0000-0002-5604-6142
Saraiva, Nuno|||0000-0003-1333-9137
Camões, Sérgio P.|||0000-0003-0355-5338
Gil, Nuno|||0000-0002-6567-8379
Rosell, Rafael|||0000-0003-0817-3400
Castro, Matilde
Miranda, Joana P.|||0000-0002-7804-4068
Oliveira, Nuno G.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Non-small cell lung cancer
Cisplatin
Apurinic/apyrimidinic endonuclease 1
E3330
Cytotoxicity
Apoptosis
Migration
Invasion
topic Non-small cell lung cancer
Cisplatin
Apurinic/apyrimidinic endonuclease 1
E3330
Cytotoxicity
Apoptosis
Migration
Invasion
description Elevated expression levels of the apurinic/apyrimidinic endonuclease 1 (APE1) have been correlated with the more aggressive phenotypes and poor prognosis of non-small cell lung cancer (NSCLC). This study aimed to assess the impact of the inhibition of the redox function of APE1 with E3330 either alone or in combination with cisplatin in NSCLC cells. For this purpose, complementary endpoints focusing on cell viability, apoptosis, cell cycle distribution, and migration/invasion were studied. Cisplatin decreased the viability of H1975 cells in a time- and concentration-dependent manner, with IC values of 9.6 µM for crystal violet assay and 15.9 µM for 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. E3330 was clearly cytotoxic for concentrations above 30 µM. The co-incubation of E3330 and cisplatin significantly decreased cell viability compared to cisplatin alone. Regarding cell cycle distribution, cisplatin led to an increase in sub-G1, whereas the co-treatment with E3330 did not change this profile, which was then confirmed in terms of % apoptotic cells. In addition, the combination of E3330 and cisplatin at low concentrations decreased collective and chemotactic migration, and also chemoinvasion, by reducing these capabilities up to 20%. Overall, these results point to E3330 as a promising compound to boost cisplatin therapy that warrants further investigation in NSCLC.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/252714
https://dx.doi.org/urn:doi:10.3390/antiox9060550
url https://ddd.uab.cat/record/252714
https://dx.doi.org/urn:doi:10.3390/antiox9060550
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv "la Caixa" Foundation https://doi.org/10.13039/100010434 PROYE18012ROSE
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
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repository.mail.fl_str_mv
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