Abstract
Dithiolethiones upregulate the expression of cancer-preventive proteins via modification of thiol residues in the Keap1-Nrf2 transcription factor complex. In addition to Keap1-Nrf2, dithiolethiones have the potential to modify a variety of cysteine-containing proteins in the cell. Such 'off target' reactions could contribute to either side effects or cancer-preventive efficacy. Evidence is presented here that cancer chemopreventive dithiolethiones inactivate protein tyrosine phosphatases via covalent, but thiol-labile, modification of active site residues. This observation may explain a number of previously reported cellular responses to dithiolethiones.