|Title:||5,7,3′-trihydroxy-3,4′-dimethoxyflavone-induced cell death in human leukemia cells is dependent on caspases and activates the MAPK pathway||Authors:||Torres, Fernando
|UNESCO Clasification:||32 Ciencias médicas
|Keywords:||G(2)-M Phase Arrest
Mammalian-Cells, et al
|Issue Date:||2010||Project:||Desarrollo de Nuevos, Mas Seguros y Mas Efectivos Compuestos Antileucemicos
Evaluación de Tdf Como Potencial Fármaco Antitumoral.
|Journal:||Molecular Carcinogenesis||Abstract:||Flavonoids are polyphenolic compounds which display a vast array of biological activities and are promising anticancer agents. In this study we investigated the effect of 5,7,3′-trihydroxy-3,4′-dimethoxyflavone (THDF) on viability of nine human tumor cell lines and found that it was highly cytotoxic against leukemia cells. THDF induced G2-M phase cell-cycle arrest and apoptosis through a caspase-dependent mechanism involving cytochrome c release, processing of multiple caspases (caspase-3, -6, -7, and -9) and cleavage of poly(ADP-ribose) polymerase. Overexpression of the protective mitochondrial proteins Bcl-2 and Bcl-xL conferred partial resistance to THDF-induced apoptosis. This flavonoid induced the phosphorylation of members of the mitogen-activated protein kinases (MAPKs) family and cell death was attenuated by inhibition of c-jun N-terminal kinases/stress-activated protein kinases (JNK/SAPK) and of extracellular signal-regulated kinases (ERK) 1/2. In the present study we report that THDF-induced cell death is mediated by an intrinsic dependent apoptotic event involving mitochondria and MAPKs, and through a mechanism independent of the generation of reactive oxygen species. The results suggest that THDF could be useful in the development of novel anticancer agents.||URI:||http://hdl.handle.net/10553/50559||ISSN:||0899-1987||DOI:||10.1002/mc.20619||Source:||Molecular Carcinogenesis[ISSN 0899-1987],v. 49 (5), p. 464-475 (Mayo 2010)|
|Appears in Collections:||Artículos|
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