RESUMO
The glutathione (GSH) S-transferase family of detoxification and signalling proteins represents a major hub for the metabolism of Selenium-derived compounds. At the same time, these compounds can be used to modulate the expression and multiple activities of GSTs and other glutathione-dependent genes, that are important aspects in both the chemoprevention and therapy of drug-resistant cancers. In this context, the isoform GSTP-1 (GSTP) appears to play a fundamental role. Besides promoting GSH-dependent detoxification of cellular electrophiles, GSTP physically interacts with a number of small molecules and cellular proteins producing regulatory effects across the main signal transduction and transcription pathways (identified as the "regulatory interactome of GSTP"). An emerging molecular mechanism behind such regulatory function is the activity of GSTP as a redox chaperonine responsible for the selective glutathionylation of protein Cys residues in the different subcellular compartments. The redox-sensitive transcription factor Nrf2 was recently identified as one of the regulatory nodes of this interactome at the interface between inflammation, adaptive stress response, and cell death pathways. The influence of Nrf2 in the stress response to cellular electrophiles and its regulatory interaction with GSTP are discussed in this review suggesting the hypothesis that this interaction may represent the actual pharmacological target of Se compounds with thiol peroxidase activity. These points are critically evaluated with a view to further development of these compounds in cancer prevention and the chemotherapy of drug-resistant tumours.