Besides catalyzing the inactivation of various electrophile-producing anticancer agents via conjugation to the tripeptide glutathione, some cytosolic proteins belonging to the glutathione transferase (formerly glutatione-S-transferase; GST) superfamily are emerging as negative modulators of stress/drug-induced cell apoptosis through the interaction with specific signaling kinases. In addition, several data link the overexpression of some GSTs, in particular GSTP1-1, to both natural and acquired resistance to various structurally unrelated anticancer drugs. Tumor overexpression of these proteins has provided a rationale for the search of GST inhibitors and GSTactivated cytotoxic prodrugs. In the present review we discuss the current structural and pharmacological knowledge of both types of GST-targeting compounds.
Glutathione transferases as targets for cancer therapy
Paolo Ruzza;
2009
Abstract
Besides catalyzing the inactivation of various electrophile-producing anticancer agents via conjugation to the tripeptide glutathione, some cytosolic proteins belonging to the glutathione transferase (formerly glutatione-S-transferase; GST) superfamily are emerging as negative modulators of stress/drug-induced cell apoptosis through the interaction with specific signaling kinases. In addition, several data link the overexpression of some GSTs, in particular GSTP1-1, to both natural and acquired resistance to various structurally unrelated anticancer drugs. Tumor overexpression of these proteins has provided a rationale for the search of GST inhibitors and GSTactivated cytotoxic prodrugs. In the present review we discuss the current structural and pharmacological knowledge of both types of GST-targeting compounds.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
