August 6/Oncology Business Week -- "Fisetin is a natural flavonol present in edible vegetables, fruits and wine at 2-160 mu g/g concentrations and an ingredient in nutritional supplements with much higher concentrations. The compound has been reported to exert anticarcinogenic effects as well as antioxidant and anti-inflammatory activity via its ability to act as an inhibitor of cell proliferation and free radical scavenger, respectively," investigators in Turku, Finland, report.
"Our cell-based high-throughput screen for small molecules that override chemically induced mitotic arrest identified fisetin as an antimitotic compound. Fisetin rapidly compromised microtubule drug-induced mitotic block in a proteasome-dependent manner in several human cell lines. Moreover, in unperturbed human cancer cells fisetin caused premature initiation of chromosome segregation and exit from mitosis without normal cytokinesis. To understand the molecular mechanism behind these mitotic errors, we analyzed the consequences of fisetin treatment on the localization and phoshorylation of several mitotic proteins. Aurora B, Bub1, BubR1 and Cenp-F rapidly lost their kinetochore/centromere localization and others became dephosphorylated upon addition of fisetin to the culture medium. Finally, we identified Aurora B kinase as a novel direct target of fisetin. The activity of Aurora B was significantly reduced by fisetin in vitro and in cells, an effect that can explain the observed forced mitotic exit, failure of cytokinesis and decreased cell viability," wrote A.L. Salmela and colleagues.
The researchers concluded, "Our data propose that fisetin perturbs spindle checkpoint signaling, which may contribute to the antiproliferative effects of the compound."
Salmela and colleagues published their study in Carcinogenesis ("Dietary Flavonoid Fisetin Induces a Forced Exit from Mitosis by Targeting the Mitotic Spindle Checkpoint." Carcinogenesis, 2009;30(6):1032-1040).
For additional information, contact M.J. Kallio, VTT Med Biotechnology, 4th Floor, Pharmac Bldg, Itainen Pitkakatu 4C, Turku 20521, Finland.
From the August 17, 2009, Prepared Foods E-dition