title: The effect of curcumin on glutathione-linked enzymes in K562 human leukemia cells.
abstract: Curcumin, an antioxidant present in the spice turmeric (Curcuma longa), has been shown to inhibit chemical carcinogenesis in animal models and has been shown to be an anti-inflammatory agent. While mechanisms of its biological activities are not understood, previous studies have shown that it modulates glutathione (GSH)-linked detoxification mechanisms in rats. In the present 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), glutathione reductase, and glucose-6-phosphate dehydrogenase activities. Gamma-glutamyl-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 curcumin-treated cells 1.3- and 1.6-fold, respectively (P = 0.05). The GST isozyme composition of K562 cells was determined as follows: 66% of GST Pl-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 induced by curcumin, as indicated by a relatively greater increase in activity toward 4HNE. Immunoprecipitation showed that GPx activity expressed by GST 5.8 contributed significantly (approximately 50%) to the total cytosolic GPx activity of K562 cells to lipid hydroperoxides. Taken together, these results suggest that GSTs play a major role in detoxification of lipid peroxidation products in K562 cells, and that these enzymes are modulated by curcumin.
authors.affiliation: Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Singhal
authors.forename: S
authors.initials: S
authors.lastname: Awasthi
authors.forename: U
authors.initials: U
authors.lastname: Pandya
authors.forename: J T
authors.initials: JT
authors.lastname: Piper
authors.forename: M K
authors.initials: MK
authors.lastname: Saini
authors.forename: J Z
authors.initials: JZ
authors.lastname: Cheng
authors.forename: Y C
authors.initials: YC
authors.lastname: Awasthi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents; D007527:Isoenzymes; D020014:K562 Cells; D007938:Leukemia / Q000201:enzymology*; D015227:Lipid Peroxidation / Q000187:drug effects; D011233:Precipitin Tests; D012643:Selenium / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D007202:Indicators and Reagents; D007527:Isoenzymes; D005979:Glutathione Peroxidase; D005978:Glutathione; D012643:Selenium; D003474:Curcumin