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

  • Anticancer Res. 2019 Apr;39(4):1893-1898. doi: 10.21873/anticanres.13297.
Eiki Hanada  1 Susumu Kageyama  2 Ryosuke Murai  1 Shigehisa Kubota  1 Hiromi Ii  3 Susumu Nakata  3 Hiroko Kita  4 Akihiro Kawauchi  1 Tokuhiro Chano  4
Affiliations
  • 1. Department of Urology, Shiga University of Medical Science, Shiga, Japan.
  • 2. Department of Urology, Shiga University of Medical Science, Shiga, Japan [email protected].
  • 3. Department of Clinical Oncology, Kyoto Pharmaceutical University, Kyoto, Japan.
  • 4. Department of Clinical Laboratory Medicine, Shiga University of Medical Science, Shiga, Japan.
Abstract

Background/aim: γ-Glutamylcyclotransferase (GGCT), a key enzyme involved in glutathione metabolism, catalyzes a specific reaction that generates 5-oxoproline and free Amino acids from the γ-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. Pro-GA 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.

Keywords
Pro-GA; bladder cancer; γ-glutamylcyclotransferase inhibitor.
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