Inhibition of Bladder Tumor Growth by the Green Tea Derivative Epigallocatechin-3-Gallate

Abstract

We evaluated the green tea derivative epigallocatechin-3-gallate (EGCG) as an intravesical agent for the prevention of transitional cell tumor implantation. In vitro studies were performed in the AY-27 rat transitional cell cancer and the L1210 mouse leukemia cell lines. Cells were exposed to increasing concentrations of EGCG for 30 minutes to 48 hours. Surviving cell colonies were then determined. A DNA ladder assay was performed in the 2 cell lines. Fisher 344 rats were used for in vivo studies with an intravesical tumor implantation model. Group 1 (12 rats) served as a control (tumor implantation and medium wash only). In group 2 (28 rats) 200 microM EGCG were instilled intravesically 30 minutes after tumor implantation. Rats were sacrificed 3 weeks following treatment. Gross and histological analyses were then performed on the bladders. At 6.0 x 104 cells per 100 mm dish a time dose dependent response was observed. After 2 hours of treatment with EGCG 100% cell lethality of the AY-27 cell line occurred at concentrations greater than 100 microM. Strong banding on the DNA ladder assay was seen with the L1210 mouse leukemia cell line. Only weak banding patterns were found in the AY-27 cell line treated with EGCG (100 and 200 microM) for 24 hours. All 12 controls were successfully implanted with tumors. In group 2 (EGCG instillation) 18 of the 28 animals (64%) were free of tumor (Fisher's exact test p = 0.001). The clonal assays showed a time dose related response to EGCG. Intravesical instillation of EGCG inhibits the growth of AY-27 rat transitional cells implanted in this model.