Blockade of γ-Glutamylcyclotransferase Enhances Docetaxel Growth Inhibition of Prostate Cancer Cells.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cellular Senescence
/ drug effects
Docetaxel
/ pharmacology
Enzyme Inhibitors
/ pharmacology
Gene Expression
Humans
Immunohistochemistry
Male
Prostatic Neoplasms
/ drug therapy
RNA, Small Interfering
/ genetics
gamma-Glutamylcyclotransferase
/ antagonists & inhibitors
docetaxel
pro-GA
prostate cancer cells
senescence
γ-glutamylcyclotransferase
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
received:
18
07
2019
revised:
23
07
2019
accepted:
24
07
2019
entrez:
15
9
2019
pubmed:
15
9
2019
medline:
27
9
2019
Statut:
ppublish
Résumé
γ-Glutamylcyclotransferase (GGCT) is highly expressed in many forms of cancer, and is a promising therapeutic target. The present study investigated whether inhibition of GGCT enhanced the antiproliferative effects of the drug docetaxel in prostate cancer cells. Immunohistochemistry and western blot analysis were conducted to measure GGCT expression in prostate cancer tissue samples and cell lines. GGCT was inhibited using RNAi and a novel enzymatic inhibitor, pro-GA, and cell proliferation was evaluated with single and combination treatments of GGCT inhibitors and docetaxel. GGCT was highly expressed in cultured prostate cancer cells and patient samples. GGCT inhibition alone inhibited prostate cancer cell line proliferation and induced cellular senescence. GGCT inhibition in combination with apoptosis-inducing docetaxel had more potent antiproliferative effects than either drug used alone. GGCT inhibition may potentiate anticancer drug efficacy.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
γ-Glutamylcyclotransferase (GGCT) is highly expressed in many forms of cancer, and is a promising therapeutic target. The present study investigated whether inhibition of GGCT enhanced the antiproliferative effects of the drug docetaxel in prostate cancer cells.
MATERIALS AND METHODS
METHODS
Immunohistochemistry and western blot analysis were conducted to measure GGCT expression in prostate cancer tissue samples and cell lines. GGCT was inhibited using RNAi and a novel enzymatic inhibitor, pro-GA, and cell proliferation was evaluated with single and combination treatments of GGCT inhibitors and docetaxel.
RESULTS
RESULTS
GGCT was highly expressed in cultured prostate cancer cells and patient samples. GGCT inhibition alone inhibited prostate cancer cell line proliferation and induced cellular senescence. GGCT inhibition in combination with apoptosis-inducing docetaxel had more potent antiproliferative effects than either drug used alone.
CONCLUSION
CONCLUSIONS
GGCT inhibition may potentiate anticancer drug efficacy.
Identifiants
pubmed: 31519583
pii: 39/9/4811
doi: 10.21873/anticanres.13666
doi:
Substances chimiques
Antineoplastic Agents
0
Enzyme Inhibitors
0
RNA, Small Interfering
0
Docetaxel
15H5577CQD
gamma-Glutamylcyclotransferase
EC 4.3.2.9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4811-4816Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.