Modulation of glutathione and related enzymes in reversal of resistance to anticancer drugs.
Eukaryotic cells have evolved several mechanisms to protect cellular constituents, especially DNA, from highly reactive molecules entering from without. The greater affinity of electrophiles for thiol groups than for hydroxyl or amine groups provides a teleologic rationale that the availability of high concentrations of thiol could be protective of these other important entities. The major intracellular nonprotein thiol is the tripeptide glutathione.
O'Dwyer
P J
PJ
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Hamilton
T C
TC
Yao
K S
KS
Tew
K D
KD
Ozols
R F
RF
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D019328:Buthionine Sulfoximine; D016466:CHO Cells; D006224:Cricetinae; D004351:Drug Resistance / Q000502:physiology; D004976:Ethacrynic Acid / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005981:Glutathione Synthase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D009363:Neoplasm Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D013852:Thiotepa / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D013852:Thiotepa; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D005981:Glutathione Synthase; D005978:Glutathione; D004976:Ethacrynic Acid