The effect of curcumin on glutathione-linked enzymes in K562 human leukemia cells

Curcumin, an antioxidant present in the spice turmeric (Curcuma longa), has been shown to inhibit chemical carcinogenesis in animal models and has bee n shown to be an anti-inflammatory agent. While mechanisms of its biologica l activities are not understood, previous studies have shown that it modula tes glutathione (GSH)-linked detoxification mechanisms in rats. In the pres ent studies, we have examined the effects of curcumin on GSH-linked enzymes in K562 human leukemia cells. One micromolar curcumin in medium (16 h) did not cause any noticeable change in glutathione peroxidase (GPx), glutathio ne reductase, and glucose-6-phosphate dehydrogenase activities. gamma-Gluta myl-cysteinyl synthetase activity was induced 1.6-fold accompanied by a 1.2 -fold increase in GSH levels. GSH S-transferase (GST) activities towards 1- chloro-2,4-dinitrobenzene, and 4-hydroxynonenal (4HNE) were increased in cu rcumin-treated cells 1.3- and 1.6-fold, respectively (P = 0.05). The GST is ozyme composition of K562 cells was determined as follows: 66% of GST P1-1, 31% of Mu class GST(s), and 3% of an anionic Alpha-class isozyme hGST 5.8, which was immunologically similar to mouse GSTA4-4 and displayed substrate preference for 4HNE. The isozyme hGST 5.8 appeared to be preferentially in duced by curcumin, as indicated by a relatively greater increase in activit y toward 4HNE. Immunoprecipitation showed that GPx activity expressed by GS T 5.8 contributed significantly (similar to 50%) to the total cytosolic GPx activity of K562 cells to lipid hydroperoxides. Taken together, these resu lts suggest that GSTs play a major role in detoxification of lipid peroxida tion products in K562 cells, and that these enzymes are modulated by curcum in. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.