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.
Highlights
About 400,000 superficial bladder cancer patients in the United States are at risk of recurrence and/or progression to invasive diseases, and in addition, numerous smokers and workers exposed to industrial carcinogens are at risk of developing primary bladder tumors [1]
We found that flavokawains and a crude kava extract induced apoptosis in bladder cancer cells, but kavalactones did not
RT4 cell line with wild-type p53 was derived from recurrent, superficial bladder tumor [24]
Summary
About 400,000 superficial bladder cancer patients in the United States are at risk of recurrence and/or progression to invasive diseases, and in addition, numerous smokers and workers exposed to industrial carcinogens are at risk of developing primary bladder tumors [1]. For these people, effective preventive measures are needed. Incidences for the three highest kava-drinking countries, such as Vanuatu, Fiji, and Western Samoa, were one fourth or one third the cancer incidences in non-kava-drinking countries, such as New Zealand (Maoris) and United States (Hawaii and Los Angeles), and nondrinking Polynesians. Given that smoking is a major risk factor for bladder cancer and that generally bladder cancer is three to four times more common in men than in women [6], these reports are very intriguing to us
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
