5,7,3'-Trihydroxy-3,4'-dimethoxyflavone inhibits the tubulin polymerization and activates the sphingomyelin pathway.

Authors:
Fernando Torres
Fernando Torres
University of Texas Southwestern Medical Center
United States
Jose Quintana
Jose Quintana
Hospital Galdakao-Usansolo (Osakidetza)-Red de Investigación en Servicios de Salud en Enfermedades Crónicas
Spain
Francisco Estevez
Francisco Estevez
Juan Canalejo Hospital
Spain

Mol Carcinog 2011 Feb 10;50(2):113-22. Epub 2010 Dec 10.

Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.

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.

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February 2011
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Mol Carcinog 2010
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