|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:||Brouard, Ignacio
Estévez Sarmiento, Francisco
Hernandez Brito, Elisa
Quintana Aguiar, José Martín
|UNESCO Clasification:||32 Ciencias médicas||Keywords:||Apoptosis
|Issue Date:||2018||Publisher:||0009-2797||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.||URI:||http://hdl.handle.net/10553/41478||ISSN:||0009-2797||DOI:||10.1016/j.cbi.2018.04.006||Source:||Chemico-Biological Interactions[ISSN 0009-2797],v. 288, p. 1-11|
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