Cellular accumulation of dietary anticarcinogenic isothiocyanates is followed by transporter-mediated export as dithiocarbamates

Abstract

Many dietary isothiocyanates (ITCs) are potent anticarcinogenic agents. ITCs rapidly accumulate to high concentrations in cells as a result of conjugation with intracellular thiols, especially glutathione (GSH). The anticarcinogenic activity of ITCs depends on, at least partly, their accumulation in cells. We report that three major anticarcinogenic ITCs, including allyl-ITC, benzyl-ITC, and phenethyl-ITC, were rapidly exported, upon accumulation in cells, mainly in the forms of GSH- and cysteinylglycine-conjugates, apparently involving MRP-1 and Pgp-1. These findings are consistent with our previous results regarding cellular export of another anticarcinogenic ITC, sulforaphane, and suggest a common cellular response to ITCs.