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Artigo Acesso aberto Produção Nacional Revisado por pares
BIBTEX RIS

Novel nitroaromatic compound activates autophagy and apoptosis pathways in HL60 cells

2017; Elsevier BV; Volume: 283; Linguagem: Inglês

10.1016/j.cbi.2017.12.012

ISSN

1872-7786

Autores

Gabriele de Matos Cardoso Perdigão, Marcela Silva Lopes, Lucas Bonfim Marques, Pedro H. D. M. Prazeres, Kamila de Sousa Gomes, Renata Barbosa de Oliveira, Mauro Cunha Xavier Pinto, Elaine M. Souza–Fagundes,

Tópico(s)

RNA Interference and Gene Delivery

Resumo

N-(2-butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (NBCN) is a nitroaromatic bioreducible compound with cytotoxic effects in cancer cell lines. The aim of this work was to investigate the molecular mechanisms involved in cell death promoted by NBCN in HL60 cells. We observed that NBCN treatment increased intracellular ROS and reduced mitochondria membrane potential (ΔΨm). NBCN treatment also induced morphological changes, phosphatidylserine exposure, cell cycle arrest in G2/M-phase, DNA condensation and fragmentation, but it did not show cytotoxic effects on normal human peripheral blood mononuclear cells (PBMCs). NBCN-induced caspase 3- and 9-dependent DNA fragmentation, which was blocked by pretreatment with the broad-spectrum caspase inhibitor, z-VAD-fmk. Flow cytometry analysis demonstrated that NBCN also increased of the number of autophagic vesicles in HL60 cells, which was not observed when cells were pre-treated with bafilomycin A1. Taken together, these results indicate that NBCN triggered the mitochondrial apoptotic pathway and led to the onset of autophagic cell death, which contributed to its cytotoxic effects.

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