Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical

• DOI: 10.1371/journal.pone.0163821
• Publication Date: 2016-09-29T20:22:37Z
• Authors: Vandana Kumari; Marzena A. Dyba; Ryan J. Holland; Yu-He Liang; Shivendra V. Singh; Xinhua Ji
• Keywords: Phenethyl isothiocyanate; Cruciferous vegetables; Myrosinase; Anticarcinogen

Dietary isothiocyanates abundant as glucosinolate precursors in many edible cruciferous vegetables are effective for prevention of cancer chemically-induced and transgenic rodent models. Some these agents, including phenethyl isothiocyanate (PEITC), have already advanced to clinical investigations. The primary route metabolism is its conjugation with glutathione (GSH), a reaction catalyzed by S-transferase (GST). pi class GST subunit type 1 (hGSTP1) much more than the alpha (hGSTA1) catalyzing conjugation. Here, we report crystal structures hGSTP1 hGSTA1 each complex GSH adduct PEITC. We find that PEITC also covalently modifies cysteine side chains GST, which irreversibly inhibits enzymatic activity.