Abstract 619: Flavokawain A inhibits urinary bladder carcinogenesis in the UPII-SV40T transgenic mouse bladder cancer model.

Abstract

Abstract The UPII-SV40T transgenic model of the mouse bladder reproduces a precursor to recurrent and invasive Transitional Cell Carcinoma (TCC): carcinoma in situ (CIS). This model therefore is useful for testing the potential of agents for preventing bladder cancer recurrence. Flavokawain A is the predominant chalcone identified from the kava plant. We have recently shown that flavokawain A exhibited strong growth inhibitory effects on human bladder cancer cell lines both in vitro in cell cultures and in vivo in a xenograft mouse model. In this study, we examine whether flavokawain A can also inhibit bladder cancer development in the UPII-SV40T transgenic model. The transgenic mice were identified through genotyping using Southern blotting analysis. Both heterozygous and homozygous UPII-SV40T mice were fed orally with vehicle control or 6 g flavokawain A /kg food for 9 months starting at 6 weeks of age. More than 54% control food- fed male mice died of ureter obstruction and nephrohydrosis within 10.5 months of age, while more than 67% of mice fed with 6g flavokawain A /kg food survived beyond 10.5 months of age. The mean bladder weight of male transgenic mice that were fed with 6g flavokawain /kg food for 9 months decreased by about 46% compared to those fed with vehicle control diet (mean bladder weights for vehicle control versus flavokawain A treatments are 0.2031±0.016 versus 0.1108±0.02565, P=0.0037). The mean bladder weights of female transgenic mice that were fed with 6g flavokawain /kg food for 9 months decreased by 31% compared to those fed with vehicle control diet (mean bladder weights for vehicle control versus flavokawain A treatments are 0.0466±0.0052 versus 0.03225±0.004689, p=0.0556). Mouse pathology analysis revealed that vehicle control treated mice exhibited poorly differentiated transitional cell carcinoma in the bladder, while that flavokawain A treated mice presented well differentiated tumors in the bladder. The bladder tissues from flavokawain A treated mice showed a decreased number of Ki67 positive cells compared to those in vehicle control treated mice, which suggested that flavokawain A inhibited cell proliferation in vivo in bladder tumors. These results suggested a potential of flavokawain A in preventing the recurrence of non-muscle invasive urinary bladder cancer by treating CIS. 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 619. doi:1538-7445.AM2012-619