Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 283, Issue -, Pages 107-115Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2017.12.012
Keywords
Nitrocompound; G2/M arrest; Apoptosis; Autophagy
Funding
- FAPEMIG (Foundation for Research Support of the State of Minas Gerais) [PPSUS CDS-APQ03458-13]
- CAPES (Coordination for the Improvement of Higher Education Personnel)
- CNPq (National Council for Scientific and Technological Development, Brazil)
- CNPq
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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 (Delta Psi m). 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 pretreated 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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