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Inhibition of γ-glutamyl transpeptidase activity decreases intracellular cysteine levels in cervical carcinoma
by
RUOSO, P
, HEDLEY, D. W
in
Animals
/ Antineoplastic agents
/ Biological and medical sciences
/ Carcinoma, Squamous Cell - physiopathology
/ Cell Line, Tumor
/ Cysteine - analysis
/ Enzyme Inhibitors - pharmacology
/ Female
/ gamma-Glutamyltransferase - antagonists & inhibitors
/ gamma-Glutamyltransferase - pharmacology
/ Humans
/ Isoxazoles - pharmacology
/ Medical sciences
/ Mice
/ Mice, SCID
/ Pharmacology. Drug treatments
/ Transplantation, Heterologous
/ Tumors
/ Uterine Cervical Neoplasms - physiopathology
2004
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Inhibition of γ-glutamyl transpeptidase activity decreases intracellular cysteine levels in cervical carcinoma
by
RUOSO, P
, HEDLEY, D. W
in
Animals
/ Antineoplastic agents
/ Biological and medical sciences
/ Carcinoma, Squamous Cell - physiopathology
/ Cell Line, Tumor
/ Cysteine - analysis
/ Enzyme Inhibitors - pharmacology
/ Female
/ gamma-Glutamyltransferase - antagonists & inhibitors
/ gamma-Glutamyltransferase - pharmacology
/ Humans
/ Isoxazoles - pharmacology
/ Medical sciences
/ Mice
/ Mice, SCID
/ Pharmacology. Drug treatments
/ Transplantation, Heterologous
/ Tumors
/ Uterine Cervical Neoplasms - physiopathology
2004
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Inhibition of γ-glutamyl transpeptidase activity decreases intracellular cysteine levels in cervical carcinoma
by
RUOSO, P
, HEDLEY, D. W
in
Animals
/ Antineoplastic agents
/ Biological and medical sciences
/ Carcinoma, Squamous Cell - physiopathology
/ Cell Line, Tumor
/ Cysteine - analysis
/ Enzyme Inhibitors - pharmacology
/ Female
/ gamma-Glutamyltransferase - antagonists & inhibitors
/ gamma-Glutamyltransferase - pharmacology
/ Humans
/ Isoxazoles - pharmacology
/ Medical sciences
/ Mice
/ Mice, SCID
/ Pharmacology. Drug treatments
/ Transplantation, Heterologous
/ Tumors
/ Uterine Cervical Neoplasms - physiopathology
2004
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Inhibition of γ-glutamyl transpeptidase activity decreases intracellular cysteine levels in cervical carcinoma
Journal Article
Inhibition of γ-glutamyl transpeptidase activity decreases intracellular cysteine levels in cervical carcinoma
2004
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Overview
To determine whether gamma-glutamyl transpeptidase (gamma-GT) is involved in the maintenance of elevated cysteine levels in cervical carcinoma.
Four cervical carcinoma cell lines were tested in vitro for cysteine accumulation and gamma-GT levels. The highest and lowest gamma-GT-expressing cell lines were used in in vivo experiments to determine the effect of gamma-GT inhibition on cysteine levels.
Treatment of a series of cervical carcinoma cell lines with acivicin decreased intracellular cysteine concentrations. Cysteine depletion was evident in Me180 cells which had the greatest levels of gamma-GT activity, and had a more pronounced cysteine decrease in medium with glutathione and cysteine concentrations simulating the in vivo situation. Also investigated were the effects of inhibition of gamma-GT activity on intracellular cysteine levels in xenografts grown in severe combined immunodeficient (SCID) mice. With the use of 35 mg/kg of acivicin, gamma-GT activity decreased to basal levels of detection in both tumour types and significant decreases in cysteine levels were seen in the high gamma-GT-expressing tumours (Me180). Thus, inhibition of gamma-GT activity may have therapeutic potential in high-expressing cancers.
In tumours and cell lines with elevated levels of gamma-GT activity, inhibition of this enzyme led to decreases of cysteine levels.
Publisher
Springer
Subject
/ Biological and medical sciences
/ Carcinoma, Squamous Cell - physiopathology
/ Enzyme Inhibitors - pharmacology
/ Female
/ gamma-Glutamyltransferase - antagonists & inhibitors
/ gamma-Glutamyltransferase - pharmacology
/ Humans
/ Mice
/ Pharmacology. Drug treatments
/ Transplantation, Heterologous
/ Tumors
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