Glutathione analogues in cancer treatment.
Glutathione is an important intracellular antioxidant and redox potential regulator that plays a vital role in drug detoxification and elimination and in cellular protection from damage by free radicals, peroxides, and toxins. Molecular alterations reported in many of the components of the glutathione system in various tumors and cancer cell lines can lead to increased survival and enhanced chemotherapy drug resistance. Several glutathione analogues that target this system have been developed and used experimentally and clinically in an attempt to improve cancer chemotherapy. These compounds include glutathione-S-transferase inhibitors and prodrugs, glyoxalase I inhibitors, and S-nitrosoglutathione. Work with these analogues has shown promising results, although lack of tumor specificity is a potential problem. Continuing development and optimization of glutathione analogues will lead to more specific targeting of this system in cancer treatment, allowing an increased therapeutic response.
Hamilton
David
D
Department of Pharmacology and Therapeutics, The Montreal Center for Experimental Therapeutics in Cancer, Room D127, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Québec, Canada H3T-1E2.
Batist
Gerald
G
D005978:Glutathione / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy*; D026422:S-Nitrosoglutathione / Q000627:therapeutic use
C099177:S-4-bromobenzylglutathione cyclopentyl diester; D026422:S-Nitrosoglutathione; D005982:Glutathione Transferase; D007791:Lactoylglutathione Lyase; D005978:Glutathione