Inactivation of protein tyrosine phosphatases by oltipraz and other cancer chemopreventive 1,2-dithiole-3-thiones

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.

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