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#B171 Flavokawain A Promotes Microtubule Polymerization in Bladder Cancer T24 Cells, and is Accompanied by G2M Arrest, Elevated Cyclin B1 Expression and CDK1 Kinase Activity.
Anne R. Simoneau,1 Dazhi Cen,2 Fang-Yao Stephen Hou,3 Xiaolin Zi.1
Department of Urology and Chao Family Comprehensive Cancer Center,1 Orange, CA, Chao Family Comprehensive Cancer Ctr.,2 Orange, CA, Developmental Biology Center, University of California at Irvine,3 Irvine, CA.
We have recently reported that flavokawain A, a novel chalcone from the extract of kava kava, induces apoptosis in human bladder carcinoma T24 cells (X. Zi et al., Proc. Am. Assoc. Cancer Res. 44 (2nd ed.) : 543, 2003).
In studies on the mechanism of its action, we found that flavokawain A caused excessive polymerization and bundling of microtubules in bladder cancer T24 cells. Flavokawain A treatment at doses of 5 to 25 ėg/ml increased polymerization of tubulin by 10% to 33%, respectively.
Analysis of cell cycle progression showed that flavokawain A treatment resulted in a significant G2M arrest, followed by an increase in the pre-G1 population (apoptotic cells).
Concomitantly, the elevated protein levels of cyclin B1 and the increased CDK1 kinase activities by flavokawain A treatment were observed in a time-dependant fashion.
Taken together, we demonstrate that flavokawain A has novel pharmacological properties that may be of use in the prevention and therapy of bladder cancers
(Supported by an unrestricted grant from Neil Chamberlain Bladder Cancer Fund and from Chao Family Comprehensive Cancer Center to X. Z.).
Frontiers in Cancer Prevention Research, 2003
AACR
Published: Cancer Res. 2005 Apr 15;65(8):3479-86.
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