[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.
Kondo
T
T
Atomic Disease Institute, Nagasaki University School of Medicine, Japan.
Iida
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy; D010453:Peptide Synthases / Q000502:physiology; D016337:RNA, Catalytic; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D016337:RNA, Catalytic; D004317:Doxorubicin; D010453:Peptide Synthases; C035550:gamma-glutamylhistamine synthetase; D005978:Glutathione; D002945:Cisplatin; D008558:Melphalan