Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death

Glutathione S-transferases (GSTs) family of enzymes is best known for their cytoprotective role and their involvement in the development of anticancer drug resistance. Recently, emergence of non-detoxifying properties of GSTs has provided them with significant biological importance. Addressing the complex interactions of GSTs with regulatory kinases will help in understanding its precise role in tumor pathophysiology and in designing GST-centered anticancer strategies. We reviewed all published literature addressing the detoxification and regulatory roles of GSTs in the altered biology of cancer and evaluating novel agents targeting GSTs for cancer therapy. The role of GSTs, especially glutathione S-transferase P1 isoform in tumoral drug resistance, has been the cause of intense debate. GSTs have been demonstrated to interact with different protein partners and modulate signaling pathways that control cell proliferation, differentiation and apoptosis. These specific functions of GSTs could lead to the development of new therapeutic approaches and to the identification of some interesting candidates for preclinical and clinical development. This review focuses on the crucial role played by GSTs in the development of resistance to anticancer agents and the major findings regarding the different modes of action of GSTs to regulate cell signaling.