Epigallocatechin-3-gallate prevents tumor cell implantation/growth in an experimental rat bladder tumor model.
The aim of this study was to determine the efficacy of epigallocatechin-3-gallate (EGCG) (Polyphenon E®) in comparison with mitomycin C (MMC) to prevent tumor cell implantation/growth in an animal model of superficial bladder cancer and search for possible mechanism(s) of action. Female Fisher 344 rats were used to study the effects of EGCG and mitomycin C for the prevention of transitional cell tumor implantation (AY-27). Twenty rats served as a control, tumor implantation and saline wash only. Sixty rats were treated with EGCG (100, 200 and 400 µM) intravesically for 60 or 120 min after tumor implantation. Thirty other rats were divided equally and pretreated with 400 µM EGCG or saline for 120 min before tumor initiation. In a separate series of experiments, 30 rats were treated 2 weeks after tumor initiation with saline or EGCG (400 µM). In a different experiment 39 rats were treated with: saline (n=10) EGCG (n=9) 400 µM, MMC (n=10) 0.5 µM, MMC (n=10) 400 µM. Rats were sacrificed 3 weeks following treatment. Gross and histological analyses were performed on the bladders. EGCG and mitomycin C prevented intravesical tumor growth in a concentration- and time-dependent manner. EGCG pretreatment or treatment 2 weeks post tumor implantation did not have therapeutic effects. Molecular modeling suggests that EGCG inhibits urokinase and matrix metalloproteinase-9. EGCG prevents intravesical tumor implantation/growth with a slightly better efficacy than mitomycin C in this experimental model. The data suggest that EGCG lowers proteolytic activity and lowers probability of cancer cell implantation rather than direct cancer cell killing.
Urology Research Center, Department of Urology, College of Medicine, University of Toledo, Toledo, OH 43614, USA.
Jerzy
J
Jankun
Rick W
RW
Keck
Steven H
SH
Selman
D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D016685:Mitomycin; D002392:Catechin; C045651:epigallocatechin gallate