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Title: 5,7,3'-trihydroxy-3,4'-dimethoxyflavone inhibits the tubulin polymerization and activates the sphingomyelin pathway
Authors: Torres, Fernando
Quintana, Jose 
Estevez, Francisco 
UNESCO Clasification: 32 Ciencias médicas
320101 Oncología
320703 Carcinogénesis
Keywords: Human Leukemia-Cells
G(2)-M Phase Arrest
Acid Sphingomyelinase
Ceramide Generation
Induced Apoptosis, et al
Issue Date: 2011
Project: Desarrollo de Nuevos, Mas Seguros y Mas Efectivos Compuestos Antileucemicos 
Journal: Molecular Carcinogenesis 
Abstract: Flavonoids are polyphenolic compounds which display a vast array of biological activities and are among the most promising anti-cancer agents. The derivative of quercetin, 5,7,3'-trihydroxy-3,4'-dimethoxyflavone (THDF), is a natural flavonoid that inhibits cell proliferation and induces apoptosis in human leukemia cells. Here we show that THDF induces cell-cycle arrest in the M phase and inhibits tubulin polymerization. This was associated with the accumulation of cyclin B1 and p21(Cip1), changes in the phosphorylation status of cyclin B1, Cdk1, Cdc25C, and MPM-2, and activation of the acidic sphingomyelinase (ASMase). Moreover, desipramine attenuated THDF-mediated cell death, indicating a crucial role of ASMase in the mechanism of cell death. In vivo studies on the athymic nude mouse xenograft model also confirmed that THDF inhibits growth of human leukemia cells and suggest that this compound may have therapeutic value.
ISSN: 0899-1987
DOI: 10.1002/mc.20693
Source: Molecular Carcinogenesis[ISSN 0899-1987],v. 50 (2), p. 113-122 (Febrero 2011)
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