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5,7,3'-Trihydroxy-3,4'-dimethoxyflavone Inhibits the Tubulin Polymerization and Activates the Sphingomyelin Pathway

5,7,3'-Trihydroxy-3,4'-dimethoxyflavone Inhibits the Tubulin Polymerization and Activates the Sphingomyelin Pathway

Fernando Torres, José Quintana, Francisco Estévez

Mol Carcinog. 2011 Feb;50(2):113-22.

PMID: 21229608

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP4143628	3′,4′-Dimethoxyflavone		4143-62-8	Price

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