A Novel Prodrug of a γ-Glutamylcyclotransferase Inhibitor Suppresses Cancer Cell Proliferation in vitro and Inhibits Tumor Growth in a Xenograft Mouse Model of Prostate Cancer

Hiromi IiTatsuhiro Yoshiki


γ-Glutamylcyclotransferase (GGCT) depletion inhibits cancer cell proliferation. However, whether the enzymatic activity of GGCT is critical for the regulation of cancer cell growth remains unclear. In this study, a novel diester-type cell-permeable prodrug, pro-GA, was developed based on the structure of N-glutaryl-l-alanine (GA), by structure optimization using temporary fluorophore-tagged prodrug candidates. The antiproliferative activity of pro-GA was demonstrated using GGCT-overexpressing NIH-3T3 cells and human cancer cells including MCF7, HL-60, and PC3 cells. By contrast, normal cells were not significantly affected by pro-GA treatment. Moreover, pro-GA administration exhibited anticancer effects in a xenograft model using immunocompromised mice inoculated with PC3 cells. These results indicate that the enzymatic activity of GGCT accelerates tumor growth and that GGCT inhibition is a promising therapeutic strategy for the treatment of GGCT-overexpressing tumors.


Feb 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·A G PalekarA Meister
Jun 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·V P WellnerA Larsson
Nov 1, 1970·Proceedings of the National Academy of Sciences of the United States of America·M Orlowski, A Meister
Aug 19, 2009·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Keisuke OdaIkuo Tooyama
Feb 1, 2007·Proteomics. Clinical Applications·Susumu KageyamaTatsuhiro Yoshiki
Oct 18, 2011·Analytical Biochemistry·Philip G Board, Inca Hutchinson
Oct 12, 2013·Chembiochem : a European Journal of Chemical Biology·Taku YoshiyaYuji Nishiuchi
Feb 5, 2015·Organic & Biomolecular Chemistry·Taku YoshiyaYuji Nishiuchi
May 6, 2015·Cancer Biotherapy & Radiopharmaceuticals·Zhifeng LinQiang Lin
May 7, 2015·International Journal of Urology : Official Journal of the Japanese Urological Association·Susumu KageyamaAkihiro Kawauchi
Sep 5, 2015·BioMed Research International·Susumu KageyamaAkihiro Kawauchi
Feb 2, 2016·Biochemical and Biophysical Research Communications·Shang-Hang ShenZhan-Xiang Wang
Jul 5, 2016·Chemical & Pharmaceutical Bulletin·Hiromi IiJun'ichi Uenishi
Feb 16, 2017·Journal of Peptide Science : an Official Publication of the European Peptide Society·Taku YoshiyaTatsuhiro Yoshiki


Dec 28, 2019·Biomolecules·Yen T K NguyenByung Woo Han

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