[gamma-GCS and glutathione--new molecular targets in cancer treatment]

Glutathione (gamma-Glutamylcysteinyl glycine, GSH) exists in almost all cells in a millimolar order of concentration. GSH plays an important role in protecting cells against oxidative stress, maintaining a reducing environment within the cells, and inactivating many xenobiotics. Synthesis of GSH is regulated by gamma-glutamylcysteine synthetase (gamma-GCS). Increase in the activity of gamma-GCS has been found in many drug-resistant cancer cells. It is believed that GSH plays a role in the aquisition of resistance to anti-cancer drugs, such as a cisplatin, adriamycin, melphalan, or taxol. In this paper, the possible mechanism of GSH involvement in drug-resistance and new approach for the depletion of GSH by suppressing the expression of gamma-GCS are introduced.