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Title: 3 '-Hydroxy-3,4 '-dimethoxyflavone-induced cell death in human leukaemia cells is dependent on caspases and reactive oxygen species and attenuated by the inhibition of JNK/SAPK
Authors: Estévez Sarmiento, Francisco 
Hernández Brito, Elisa 
Brouard Martín,Ignacio 
León, Francisco
García, Celina
Quintana Aguiar, José Martín 
Estévez, Francisco 
UNESCO Clasification: 32 Ciencias médicas
Keywords: Apoptosis
Cell cycle
Issue Date: 2018
Journal: Chemico-biological interactions (Print) 
Abstract: Flavonoids are phenolic substances that appear to exert beneficial effects in several chronic diseases, including cancer. Structure-activity relationships of the cytotoxic activity of a series of flavonols and their 3-methyl ether derivatives established that 3′-hydroxy-3,4′-dimethoxyflavone (flavonoid 11) displayed strong cytotoxicity against human leukaemia cell lines (HL-60, U-937 and MOLT-3), and cells that over-express the anti-apoptotic proteins, Bcl-2 and Bcl-xL, and against P-glycoprotein-overexpressing K-562/ADR cells. This compound induced G2-M cell cycle arrest and it was a potent apoptotic inducer on HL-60, MOLT-3, U-937 and U-937/Bcl-2 cell lines. Cell death was (i) mediated by caspase activation, since it was prevented by the non-specific caspase inhibitor z-VAD-fmk and reduced by a selective caspase-9 inhibitor, (ii) associated with cytochrome c release, the dissipation of the inner mitochondrial membrane potential (ΔΨm) and the activation of the mitogen-activated protein kinase pathway and (iii) partially blocked by the inhibition of c-jun NH2terminal kinases/stress activated protein kinases (JNK/SAPK) signalling and by the free-radical scavenger N-acetyl-L-cysteine.
ISSN: 0009-2797
DOI: 10.1016/j.cbi.2018.04.006
Source: Chemico-Biological Interactions [ISSN 0009-2797], v. 288, p. 1-11, (Mayo 2018)
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