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 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.
Singhal
S S
SS
Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555, USA.
Awasthi
S
S
Pandya
U
U
Piper
J T
JT
Saini
M K
MK
Cheng
J Z
JZ
Awasthi
Y C
YC
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
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D007202:Indicators and Reagents; D007527:Isoenzymes; D005979:Glutathione Peroxidase; D005978:Glutathione; D012643:Selenium; D003474:Curcumin