Chemoprevention Of Hydroxybutyl(Butyl)Nitrosamine (Oh-Bbn)-Induced Mouse Urinary Bladder Cancer By The Kava Chalcone Flavokawain A

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL About 75% of human bladder cancers are associated with cigarette smoking or exposure to industrial carcinogens. Kava roots have been traditionally used to prepare beverage and herb medicine in the South Pacific Island nations (Fiji, Vanutu, Samoa, etc.) for thousands of years. Recently, an epidemiological study has linked high kava consumption to lower incidences of cancers, including lung and bladder cancers, despite the presence of many smokers in the populations of the South Pacific Islands. We therefore examined the potential of flavokawain A, a predominant chalcone isolated from the kava plant for prevention of mouse urinary bladder cancer induced by the organ-specific and tobacco-smoking related nitrosamine OH-BBN. B6D2F1 mice at 8 weeks of age were gavaged 7.5 mg OH-BBN once per week for 12 weeks. In the standard prevention protocol, 0.1% FKA or vehicle food was administered as a dietary supplement to each group of mice beginning 1 week before the first OH-BBN administration and ending 32 weeks after the initial OH-BBN treatment. Dietary feeding of OH-BBN treated mice with 0.1% flavokawain A in the mouse diet decreased bladder wet weight by about 57% (Bladder weights for control versus flavokawain A were 74.18 ± 16.7 versus 32 ± 1.5 mg; P<0.01). In the standard promotion protocol, 0.1% FKA or vehicle food was given 1 week after the final OH-BBN administration for 19 weeks. Flavokawain A also significant reduced the bladder wet weight by about 27% (Bladder weights for control versus flavokawain A were 89.4 ± 23.4 versus 65.5 ± 10.6 mg; p<0.05). To increase the incidence of palpable OH-BBN induced bladder tumors, we extended 7.5mg OH-BBN treatment once per week for one more week up to a total of 13 weeks. In this modified promotion protocol, the percentage of palpable tumors in control group has reached to about 53%, which is similar to that reported by published literatures. Dietary feeding of 0.6% flavokawain A significantly decrease bladder wet weight by 73% (Bladder weights for control versus flavokawain A were 314.9 ± 106.7 versus 87.3 ± 15.2 mg, p=0.0265). In addition, we showed that flavokawain A induced activities of phase II enzyme (i.e. glutathione S-transferase and quinone reductase) in different organs (bladder, liver, prostate, etc.) of mice. Taken together, these results suggest that flavokawain A deserves further investigation for bladder cancer chemoprevention by targeting smoking or carcinogens exposed populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 620. doi:1538-7445.AM2012-620