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
Manguinhas, Rita (Universidade de Lisboa)
Fernandes, Ana S. (Universidade Lusófona de Humanidades e Tecnologias, Lisboa)
Costa, João G. (Universidade Lusófona de Humanidades e Tecnologias, Lisboa)
Saraiva, Nuno (Universidade Lusófona de Humanidades e Tecnologias, Lisboa)
Camões, Sérgio P. (Universidade de Lisboa)
Gil, Nuno (Lung Cancer Unit, Champalimaud Centre for the Unknown, Lisboa)
Rosell, Rafael (Universitat Autònoma de Barcelona. Departament de Medicina)
Castro, Matilde (Universidade de Lisboa)
Miranda, Joana P. (Universidade de Lisboa)
Oliveira, Nuno G. (Universidade de Lisboa)

Date:	2020
Abstract:	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.
Grants:	"la Caixa" Foundation PROYE18012ROSE
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Non-small cell lung cancer ; Cisplatin ; Apurinic/apyrimidinic endonuclease 1 ; E3330 ; Cytotoxicity ; Apoptosis ; Migration ; Invasion
Published in:	Antioxidants, Vol. 9 (june 2020) , ISSN 2076-3921

DOI: 10.3390/antiox9060550
PMID: 32599967

18 p, 4.5 MB

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Articles > Research articles
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