Mammalian glutathione S-transferase: regulation of an enzyme system to achieve chemotherapeutic efficacy.
The glutathione S-transferases are a family of Phase II detoxication enzymes that catalyze the conjugation of glutathione to a large variety of electrophilic compounds. In the 1990s, there have been many advances regarding the function of these enzymes in protecting a cell from the toxic effects of these electrophiles. The complexity of this enzyme family has been realized and much work has been performed to identify the specific roles played by individual isozymes in resistance to a variety of agents. Likewise, the determination of the crystal structure of these enzymes has allowed the identification of specific amino acid residues that are involved in the catalysis of important reactions. The important role that these enzymes play in carcinogenesis and in drug resistance has warranted an attempt to bring together these different subfields of glutathione S-transferase biology to investigate possible ways that this system could be regulated in therapeutically useful ways. In this report, we have reviewed the recent advances and ways in which this knowledge could be utilized in the advancement of the treatment of cancer.
Gulick
A M
AM
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.
Fahl
W E
WE
D000477:Alkylating Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000378:metabolism; D004351:Drug Resistance; D004789:Enzyme Activation; D015316:Genetic Therapy; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D011355:Prodrugs / Q000627:therapeutic use; D015262:Xenobiotics / Q000378:metabolism
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D002273:Carcinogens; D011355:Prodrugs; D015262:Xenobiotics; D005982:Glutathione Transferase; D005978:Glutathione