1. Role of GST P1-1 in mediating the effect of etoposide on human neuroblastoma cell line Sh-Sy5y.
- Author
-
Bernardini S, Bellincampi L, Ballerini S, Ranalli M, Pastore A, Cortese C, and Federici G
- Subjects
- Blotting, Western, Clone Cells drug effects, Clone Cells metabolism, Clone Cells pathology, Drug Resistance, Neoplasm, Glutathione pharmacology, Glutathione S-Transferase pi, Glutathione Transferase genetics, Humans, Isoenzymes genetics, Tumor Cells, Cultured, Apoptosis drug effects, Etoposide pharmacology, Gene Expression Regulation, Enzymologic drug effects, Glutathione analogs & derivatives, Glutathione Transferase metabolism, Isoenzymes metabolism, Neuroblastoma enzymology, Oxidative Stress drug effects
- Abstract
The oxidative stress could have a dual action on glutathione S-transferase (GST) P1-1 metabolism: transcriptional induction and/or polymerization. The former should represent a form of adaptation to oxidative stress and contribute to protect the cell, the latter one should activate apoptosis via c-Jun N-terminal kinase (JNK). We studied the effect of etoposide on human neuroblastoma cell line SH-SY5Y and on an etoposide-resistant clone to investigate whether a pleiotropic effect of etoposide on the redox status of the cell exists which is able to interfere with apoptosis through the GST P1-1 system. Etoposide treatment was able to induce GST P1-1 polymerization and activation of apoptosis. The data obtained from our etoposide-resistant clone and the possibility to reverse the sensitive phenotype to a resistant one by means of hexyl-glutathione preincubation, seem to suggest that cellular levels of glutathione have a key role in protecting GST P1-1 by oxidation and consequently the cell's decision between life and death., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF