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Título : Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species
Autor : 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 
Fecha de publicación : 2013
Editorial : Elsevier
Cita : Di Rosso ME, Barreiro Arcos ML, Elingold I, et al. Novel o-naphthoquinones induce apoptosis of EL-4 T lymphoma cells through the increase of reactive oxygen species [en línea]. Postprint del artículo publicado en Toxicology in Vitro. 2013;27(7):2094-2104. doi:10.1016/j.tiv.2013.08.002 Disponible en:
Resumen : 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.
ISSN : 0887-2333 (impreso)
1879-3177 (online)
Disciplina: MEDICINA
DOI: 10.1016/j.tiv.2013.08.002
Derechos: Acceso abierto
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