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Flavokawain A, a Novel Chalcone From Kava Extract, Induces Apoptosis in Bladder Cancer Cells by Involvement of Bax Protein-Dependent and Mitochondria-Dependent Apoptotic Pathway and Suppresses Tumor Growth in Mice

Flavokawain A, a Novel Chalcone From Kava Extract, Induces Apoptosis in Bladder Cancer Cells by Involvement of Bax Protein-Dependent and Mitochondria-Dependent Apoptotic Pathway and Suppresses Tumor Growth in Mice

Xiaolin Zi, Anne R Simoneau

Cancer Res. 2005 Apr 15;65(8):3479-86.

PMID: 15833884

Abstract:

Consumption of the traditional kava preparation was reported to correlate with low and uncustomary gender ratios (more cancer in women than men) of cancer incidences in three kava-drinking countries: Fiji, Vanuatu, and Western Samoa. We have identified flavokawain A, B, and C but not the major kavalactone, kawain, in kava extracts as causing strong antiproliferative and apoptotic effect in human bladder cancer cells. Flavokawain A results in a significant loss of mitochondrial membrane potential and release of cytochrome c into the cytosol in an invasive bladder cancer cell line T24. These effects of flavokawain A are accompanied by a time-dependent decrease in Bcl-x(L), a decrease in the association of Bcl-x(L) to Bax, and an increase in the active form of Bax protein. Using the primary mouse embryo fibroblasts Bax knockout and wild-type cells as well as a Bax inhibitor peptide derived from the Bax-binding domain of Ku70, we showed that Bax protein was, at least in part, required for the apoptotic effect of flavokawain A. In addition, flavokawain A down-regulates the expression of X-linked inhibitor of apoptosis and survivin. Because both X-linked inhibitor of apoptosis and survivin are main factors for apoptosis resistance and are overexpressed in bladder tumors, our data suggest that flavokawain A may have a dual efficacy in induction of apoptosis preferentially in bladder tumors. Finally, the anticarcinogenic effect of flavokawain A was evident in its inhibitory growth of bladder tumor cells in a nude mice model (57% of inhibition) and in soft agar.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP37951136	Flavokawain A		37951-13-6	Price

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