Cisplatin induced gamma-glutamyltransferase up-regulation, hypertrophy and differentiation in astrocytic glioma cells in culture
Language English Country Spain Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
12792879
DOI
10.14670/hh-18.687
Knihovny.cz E-resources
- MeSH
- Apoptosis MeSH
- Astrocytes cytology pathology MeSH
- Cell Differentiation MeSH
- Cell Division MeSH
- Time Factors MeSH
- Cisplatin pharmacology MeSH
- gamma-Glutamyltransferase biosynthesis MeSH
- Glioma metabolism pathology MeSH
- Glial Fibrillary Acidic Protein metabolism MeSH
- Immunohistochemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Tumor Cells, Cultured MeSH
- Antineoplastic Agents pharmacology MeSH
- Flow Cytometry MeSH
- Up-Regulation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cisplatin MeSH
- gamma-Glutamyltransferase MeSH
- Glial Fibrillary Acidic Protein MeSH
- Antineoplastic Agents MeSH
Gamma-glutamyltransferase (GGT) hydrolyses gamma-glutamylated peptides, including glutathione and transports amino acids into the cells. The enzyme is up-regulated in some tumors, especially those with a higher degree of malignancy and resistance to cytostatics. In this study we examined the effects of Cisplatin (1.6 x 10(-5)M) on the activity of GGT in astrocytic C6 glioma cells in cultures monitored for growth, morphology and differentiation. Initially (24 h), the drug inhibited cell division and later (96 h), it caused apoptotic death of about half of the population. The more resistant and surviving cells became hypertrophic and more differentiated, as indicated by their larger size and higher protein content, including the maturation- specific GFAP. In addition, the activity of GGT was significantly elevated in these cells at 48 h and onwards. At 96 h, the biochemically determined enzyme activity was between 230% and 330% above the controls. Compared to the protein content, the GGT activity started to increase later (48 h) but it grew steeper towards 72-96 h. Similarly, histochemical analysis revealed a manifold increase in the number of GGT+ cells in the population and higher intensity of staining per cell from at 48 h and onwards. The study showed that the transformed astrocytic cells can up-regulate GGT activity as part of an adaptation and/or, survival-enhancing reaction triggered by Cisplatin.
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