+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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

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

Chemmedchem 13(2): 155-163

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.

(PDF emailed within 0-6 h: $19.90)

Accession: 048135671

Download citation: RISBibTeXText

PMID: 29316360

DOI: 10.1002/cmdc.201700660

Related references

Small molecule tolfenamic acid inhibits PC-3 cell proliferation and invasion in vitro, and tumor growth in orthotopic mouse model for prostate cancer. Prostate 72(15): 1648-1658, 2012

Penta-1,2,3,4,6-O-galloyl-beta-D-glucose induces p53 and inhibits STAT3 in prostate cancer cells in vitro and suppresses prostate xenograft tumor growth in vivo. Molecular Cancer Therapeutics 7(9): 2681-2691, 2008

AIM2 suppresses human breast cancer cell proliferation in vitro and mammary tumor growth in a mouse model. Molecular Cancer Therapeutics 5(1): 1-7, 2006

Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Molecular Cancer Therapeutics 8(2): 315-323, 2009

Hinokitiol inhibits cell growth through induction of S-phase arrest and apoptosis in human colon cancer cells and suppresses tumor growth in a mouse xenograft experiment. Journal of Natural Products 76(12): 2195-2202, 2014

Lycium barbarum polysaccharides induce apoptosis in human prostate cancer cells and inhibits prostate cancer growth in a xenograft mouse model of human prostate cancer. Journal of Medicinal Food 12(4): 695-703, 2009

Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo. Oncotargets and Therapy 7: 1761-1768, 2014

Monoclonal antibody against prostate stem cell antigen inhibits prostate cancer growth and metastasis in a murine xenograft model of prostate cancer. Journal of Urology 165(5 Supplement): 46, 2001

The STAT3 Inhibitor Galiellalactone Effectively Reduces Tumor Growth and Metastatic Spread in an Orthotopic Xenograft Mouse Model of Prostate Cancer. European Urology 69(3): 400-404, 2016

Pro-GA, a Novel Inhibitor of γ-Glutamylcyclotransferase, Suppresses Human Bladder Cancer Cell Growth. Anticancer Research 39(4): 1893-1898, 2019

Absence of 5-alpha-reductase in the prostate cancer xenograft CWR22 and prostate cancer cell lines LNCaP, DU145, and MLC-SV40 Failure of finasteride to affect the in vitro growth of CWR22 prostate cancer xenograft. Surgical Forum 47(0): 820-822, 1996

shRNA-mediated insulin-like growth factor I receptor gene silencing inhibits cell proliferation, induces cell apoptosis, and suppresses tumor growth in non-small cell lung cancer: in vitro and in vivo experiments. Zhonghua Yi Xue Za Zhi 87(21): 1506-1509, 2007

α-Pinene Inhibits Human Prostate Cancer Growth in a Mouse Xenograft Model. ChemoTherapy 63(1): 1-7, 2017

siRNA-based targeting of cyclin E overexpression inhibits breast cancer cell growth and suppresses tumor development in breast cancer mouse model. Plos One 5(9): E12860, 2011

Prostate-derived Ets transcription factor (PDEF) downregulates survivin expression and inhibits breast cancer cell growth in vitro and xenograft tumor formation in vivo. Breast Cancer Research and Treatment 102(1): 19-30, 2006