{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T10:42:03Z","timestamp":1766486523026,"version":"build-2065373602"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/04138\/2019, UID\/DTP\/04567\/2019, PD\/BD\/114280\/2016, TUBITAK\/003\/2014 and PTDC\/MED-TOX\/29183\/2017"],"award-info":[{"award-number":["UID\/DTP\/04138\/2019, UID\/DTP\/04567\/2019, PD\/BD\/114280\/2016, TUBITAK\/003\/2014 and PTDC\/MED-TOX\/29183\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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 IC50 values of 9.6 \u00b5M for crystal violet assay and 15.9 \u00b5M 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 \u00b5M. 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.<\/jats:p>","DOI":"10.3390\/antiox9060550","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T02:25:16Z","timestamp":1593051916000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["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"],"prefix":"10.3390","volume":"9","author":[{"given":"Rita","family":"Manguinhas","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-0641","authenticated-orcid":false,"given":"Ana S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Research Center for Biosciences &amp; Health Technologies (CBIOS), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-6142","authenticated-orcid":false,"given":"Jo\u00e3o G.","family":"Costa","sequence":"additional","affiliation":[{"name":"Research Center for Biosciences &amp; Health Technologies (CBIOS), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-9137","authenticated-orcid":false,"given":"Nuno","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Research Center for Biosciences &amp; Health Technologies (CBIOS), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-5338","authenticated-orcid":false,"given":"S\u00e9rgio P.","family":"Cam\u00f5es","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6567-8379","authenticated-orcid":false,"given":"Nuno","family":"Gil","sequence":"additional","affiliation":[{"name":"Lung Cancer Unit, Champalimaud Centre for the Unknown, Av. Bras\u00edlia, 1400-038 Lisboa, Portugal"}]},{"given":"Rafael","family":"Rosell","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, Institute for Health Science Research Germans Trias i Pujol (IGTP), Campus Can Ruti, Ctra de Can Ruti, Cam\u00ed de les Escoles, s\/n, 08916 Badalona, Barcelona, Spain"},{"name":"Internal Medicine Department, Universitat Aut\u00f3noma de Barcelona, Campus de la UAB, Pla\u00e7a C\u00edvica, 08193 Bellaterra, Barcelona, Spain"}]},{"given":"Matilde","family":"Castro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7804-4068","authenticated-orcid":false,"given":"Joana P.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]},{"given":"Nuno G.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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