Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species

Abstract: Novel β-lapachone analogs 2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ1), 2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ3) and 2-methyl-2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ7), which have trypanocidal activity, were assayed for cytotoxic effects on murin...

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Detalles Bibliográficos
Autores principales: Di Rosso, María Emilia, Barreiro Arcos, María Laura, Elingold, Igal, Sterle, Helena Andrea, Baptista Ferreira, Sabrina, Ferreira, Vitor Francisco, Galleano, Mónica, Cremaschi, Graciela A., Dubin, Marta
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2019
Materias:
APOPTOSIS
BENZODIAZEPINAS
OXIGENO
IONES
RADICALES LIBRES
CELULAS
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8780
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8780
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic APOPTOSIS
BENZODIAZEPINAS
OXIGENO
IONES
RADICALES LIBRES
CELULAS
spellingShingle APOPTOSIS
BENZODIAZEPINAS
OXIGENO
IONES
RADICALES LIBRES
CELULAS
Di Rosso, María Emilia
Barreiro Arcos, María Laura
Elingold, Igal
Sterle, Helena Andrea
Baptista Ferreira, Sabrina
Ferreira, Vitor Francisco
Galleano, Mónica
Cremaschi, Graciela A.
Dubin, Marta
Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
topic_facet APOPTOSIS
BENZODIAZEPINAS
OXIGENO
IONES
RADICALES LIBRES
CELULAS
description Abstract: Novel β-lapachone analogs 2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ1), 2-p-tolyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ3) and 2-methyl-2-phenyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione (NQ7), which have trypanocidal activity, were assayed for cytotoxic effects on murine EL-4 T lymphoma cells. The NQs inhibited the proliferation of EL-4 cells at concentrations above 1μM. Nuclear staining of the EL-4 cells revealed chromatin condensation and a nuclear morphology compatible with the induction of apoptosis. Flow cytometry assays with annexin V-FITC and propidium iodide confirmed the cell death by apoptosis. Using electron paramagnetic resonance (EPR), a semiquinone radical was detected in EL-4 cells treated with NQs. In addition, a decrease in the GSH level in parallel with reactive oxygen species (ROS) production was observed. Preincubation with n-acetyl-l-cysteine (NAC) was able to reverse the inhibitory effects of the NQs on cell proliferation, indicating that ROS generation is involved in NQ-induced apoptosis. In addition, the NQs induced a decrease in the mitochondrial membrane potential and increased the proteolytic activation of caspases 9 and 3 and the cleavage of Poly (ADP-Ribose) Polymerase (PARP). In conclusion, these results indicate that redox cycling is induced by the NQs in the EL-4 cell line, with the generation of ROS and other free radicals that could inhibit cellular proliferation as a result of the induction of the intrinsic apoptosis pathway.
format Artículo
author Di Rosso, María Emilia
Barreiro Arcos, María Laura
Elingold, Igal
Sterle, Helena Andrea
Baptista Ferreira, Sabrina
Ferreira, Vitor Francisco
Galleano, Mónica
Cremaschi, Graciela A.
Dubin, Marta
author_facet Di Rosso, María Emilia
Barreiro Arcos, María Laura
Elingold, Igal
Sterle, Helena Andrea
Baptista Ferreira, Sabrina
Ferreira, Vitor Francisco
Galleano, Mónica
Cremaschi, Graciela A.
Dubin, Marta
author_sort Di Rosso, María Emilia
title Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
title_short Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
title_full Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
title_fullStr Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
title_full_unstemmed Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
title_sort novel o-naphthoquinones induce apoptosis of el-4 t lymphoma cells through the increase of reactive oxygen species
publisher Elsevier
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8780
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