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Title: Studies of the selective modulation of thiol level in normal and tumor cells in order to achieve a therapeutic effect

Abstract:

The aim of the studies was to utilize differences in the activity and role of γ-glutamyl transpeptidase (γGT) and γ-cystathionase (γCT) in normal and tumor cells in order to increase safety and efficiency of anticancer therapies. It was demonstrated that cystathionine, which is a CT substrate, corrected thiol antioxidant defense in normal liver and kidney cells in EAT-bearing mice. It also protected the liver against doxorubicin toxicity without diminishing cytotoxicity of the drug for EAT cells. In addition, cystathionine corrected EAT-induced disturbances in anaerobic sulfur metabolism in the kidney (but not in the liver). GT inhibitors (1,2,3,4-tetrahydroisoquinoline and acivicin) decreased cysteine level and disordered thiol antioxidant defense in EAT cells. In normal liver and kidney cells, they elevated cysteine level, decreased ROS and augmented sulfane sulfur biosynthesis. This means that EAT cells, in contrast to normal liver and kidney cells, are completely dependent on cysteine supply from the reaction catalyzed by γ-glutamyl transpeptidase. In HepG2 cells, GT inhibitors impaired cell vitality and increased doxorubicin cytotoxicity, which was observed in spite of the concomitant rise in GSH concentration.

Level of degree:

2 - studia doktoranckie

Degree discipline:

onkologia ; biochemia

Degree grantor:

Wydział Farmacji

Promoter:

Lidia Włodek

Date issued:

2008

Format:

text/html

Identifier:

oai:dl.cm-uj.krakow.pl:879

Call number:

ZB-109867

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Access rights:

tylko w bibliotece

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego - Collegium Medicum

Object collections:

Last modified:

Sep 4, 2019

In our library since:

Nov 21, 2012

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All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/879

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ZB-109867 Sep 4, 2019
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