Pro-GA, a Novel Inhibitor of γ-Glutamylcyclotransferase, Suppresses Human Bladder Cancer Cell Growth

Background/Aim: gamma-Glutamylcyclotransferase GGCT), a key enzyme involved in glutathione metabolism, catalyzes a specific reaction that generates 5-oxoproline and free amino acids from the gamma-glutamyl peptide. Inhibition of GGCT is a promising therapeutic strategy for the treatment of various cancers. Materials and Methods: Immuno-histochemistry was used to evaluate GGCT expression in bladder tumors. The growth inhibitory effect of pro-GA, a novel GGCT inhibitor, in the presence or absence of mitomycin C MMC) was assessed in three distinct bladder cancer cell lines. Results: Over half of the clinical bladder tumor samples overexpressed GGCT. ProGA reduced the growth of all bladder cancer cell lines in a dose-dependent manner, and increased the anti-tumor effect of MMC. Conclusion: Inhibition of GGCT using pro-GA provides a novel therapeutic strategy for the treatment of bladder cancers.