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6′-Benzyloxy-4-bromo-2′-hydroxychalcone is cytotoxic against human leukaemia cells and induces caspase-8- and reactive oxygen species-dependent apoptosis

AuthorsSaavedra, Ester; Del Rosario, Henoc; Brouard, Ignacio ; Quintana, José; Estévez, Francisco
Issue Date25-Jan-2019
CitationChemico-Biological Interactions 298: 137-145 (2019)
AbstractIn this study, we investigated the effects of synthetic 6′-benzyloxy-4-bromo-2′-hydroxychalcone on viabilities of seven human leukaemia cells. It was cytotoxic against U-937, HL-60, K-562, NALM-6, MOLT-3 cells, and also against Bcl-2-overexpressing U-937/Bcl-2 cells and P-glycoprotein-overexpressing K-562/ADR, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. This chalcone is a potent apoptotic inducer in human leukaemia U-937 cells. Cell death was (i) mediated by the activation and the cleavage of initiator and executioner caspases and poly(ADP-ribose) polymerase; (ii) prevented by the pan-caspase inhibitor z-VAD-fmk, and by the selective caspase-3/7, −6 and −8 inhibitors, and by a cathepsins B/L inhibitor; (iii) associated with the release of mitochondrial proteins, including cytochrome c and Smac/DIABLO; (iv) accompanied by dissipation of the mitochondrial membrane potential, (v) partially blocked by the inhibition of p38 and (vi) mostly abrogated by catalase. In conclusion, the synthetic chalcone is cytotoxic against several types of human leukaemia cell with apoptosis being induced by activation of the extrinsic pathway and the generation of reactive oxygen species.
Publisher version (URL)https://www.sciencedirect.com/science/article/pii/S0009279718309773?via%3Dihub
Identifiersdoi: 10.1016/j.cbi.2018.12.010
e-issn: 1872-7786
issn: 0009-2797
Appears in Collections:(IPNA) Artículos
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