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5,7,3′‐trihydroxy‐3,4′‐dimethoxyflavone inhibits the tubulin polymerization and activates the sphingomyelin pathway
Author(s) -
Torres Fernando,
Quintana José,
Estévez Francisco
Publication year - 2011
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20693
Subject(s) - biology , cell growth , cell cycle , cyclin dependent kinase 1 , cell cycle checkpoint , apoptosis , microbiology and biotechnology , programmed cell death , cancer cell , biochemistry , cancer research , cancer , genetics
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. © 2010 Wiley‐Liss, Inc.