Effects of flavopiridol on Cdk2 activity in cultured cell lines
Matthews, Donald Grant
Master of Science
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Flavopiradol reduced cyclin-dependent kinase activity by competititve inhibition with ATP by binding to the ATP-binding pocket of these cell cycle regulators ... it was thought that flavopiradol would be an excllent inhibitor of cell proliferation and effective tumor suppressor ... Although apoptosis was not observed after a 24hr incubation period, the antiapoptotic protein Bcl-2 was downregulated. Our findings illustrate an alternate mechanism of cdk2 inhibition in vitro, through p21 WAF1/CIP1 upregulation, showing that drugs that were shown to have specific activities when assayed using purified systems may have multiple in vivo activities and these activities differ depending on the cells used. These different effects may contribute to the variable results seen in clinical trials.