Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives

alpha -Tocopherol inhibits glutathione S-transferase p1-1 (GST P1-1) (R.I.M . van Haaften, C.T.A. Evelo. G.R.M.M. Haenen, A. East, Biochem. Biophys. Re s. Commun. 280 (2001)). In various cosmetic and dietary products a-tocopher ol is added as a tocopherol ester. Therefore we have studied the effect of various tocopherol derivatives on GST P1-1 activity. It was found that CST P1-1 is inhibited, in a concentration dependent manner, by these compounds. Of the compounds tested, the tocopherols were the most potent inhibitors o f GST P1-1. the concentration giving 50% inhibition (IC50) is < 1 muM. The esterified tocopherols and alpha -tocopherol quinone also inhibit the GST P 1-1 activity at a very low concentration: for most compounds the IC50 was b elow 10 muM RRR-alpha -Tocopherol acetate lowered the V-max values, but did not affect the K-m, for either 1-chloro-2,4-dinitrobenzene or GSH. This in dicates that the GST P1-1 enzyme is non-competitively inhibited by RRR-alph a -tocopherol acetate. The potential implications of GST P1-1 inhibition by tocopherol and alpha -tocopherol derivatives are discussed. (C) 2001 Elsev ier Science B.V. All rights reserved.