Glutathione-related mechanisms in cellular resistance to anticancer drugs.
Glutathione conjugation and transport of glutathione conjugates of anticancer drugs out of cells have been shown to work as a system in the detoxification of many anticancer drugs. The major components of this system include glutathione (GSH), GSH-related enzymes and glutathione conjugate export pump (GS-X pump). GSH can combine with anticancer drugs to form less toxic and more water soluble GSH conjugates, the conjugation reaction is catalysed by glutathione S-transferases (GSTs). The GSH conjugates of anticancer drugs can be exported from cells by GS-X pump or multidrug resistance-associated protein (MRP). GSH, glutathione-related enzymes and GS-X pump or MRP have been found to be increased or overexpressed in many drug resistant cells. Increased detoxification of anticancer drugs by this system may confer drug resistance. Inhibition of this detoxification system is a strategy for modulation of drug resistance.
Zhang
K
K
Department of Experimental Surgery, BLK 9, Level 2, Singapore General Hospital, Outram Road, Singapore, 169608, Republic of Singapore.
Mack
P
P
Wong
K P
KP
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D002352:Carrier Proteins / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D005978:Glutathione; D005982:Glutathione Transferase; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C086860:glutathione transporter