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5,7,3′-trihydroxy-3,4′-dimethoxyflavone inhibits the tubulin polymerization and activates the sphingomyelin pathway

✍ Scribed by Fernando Torres; José Quintana; Francisco Estévez

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
340 KB
Volume
50
Category
Article
ISSN
0899-1987

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✦ Synopsis

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 0 -trihydroxy-3,4 0 -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.

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