Pro-GA, a Novel Inhibitor of γ-Glutamylcyclotransferase, Suppresses Human Bladder Cancer Cell Growth.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ pharmacology
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Enzyme Inhibitors
/ pharmacology
Female
Humans
Male
Middle Aged
Mitomycin
/ pharmacology
Signal Transduction
/ drug effects
Urinary Bladder Neoplasms
/ drug therapy
gamma-Glutamylcyclotransferase
/ antagonists & inhibitors
Pro-GA
bladder cancer
γ-glutamylcyclotransferase inhibitor
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
23
02
2019
revised:
10
03
2019
accepted:
12
03
2019
entrez:
7
4
2019
pubmed:
7
4
2019
medline:
23
4
2019
Statut:
ppublish
Résumé
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. 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. 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. Inhibition of GGCT using pro-GA provides a novel therapeutic strategy for the treatment of bladder cancers.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
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
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
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
CONCLUSIONS
Inhibition of GGCT using pro-GA provides a novel therapeutic strategy for the treatment of bladder cancers.
Identifiants
pubmed: 30952730
pii: 39/4/1893
doi: 10.21873/anticanres.13297
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
GGCT protein, human
0
Mitomycin
50SG953SK6
gamma-Glutamylcyclotransferase
EC 4.3.2.9
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1893-1898Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.