Glutathione conjugates and their synthetic derivatives as inhibitors of glutathione-dependent enzymes involved in cancer and drug resistance.
Alterations in levels of glutathione (GSH) and glutathione-dependent enzymes have been implicated in cancer and multidrug resistance of tumor cells. The activity of a number of these, the multidrug resistance-associated protein 1, glutathione S-transferase, DNA-dependent protein kinase, glyoxalase I, and gamma-glutamyl transpeptidase, can be inhibited by GSH-conjugates and synthetic analogs thereof. In this review we focus on the function of these enzymes and carriers in cancer and anti-cancer drug resistance, in relation to their inhibition by GSH-conjugate analogs.
Burg
Danny
D
Division of Toxicology, Leiden/Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55 2333CC, Leiden, The Netherlands. d.burg@lacdr.leidenuniv.nl
Mulder
Gerard J
GJ
D000818:Animals; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*
D004791:Enzyme Inhibitors; D005978:Glutathione