Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action.
This study is to investigate the effect of curcumin on the induction of glutathione S-transferases (GST) and NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) were detected by Western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Treatment of HT-29 human colon adenocarcinoma cells with curcumin dramatically induced the activity of GST and NQO at the range of 10-30 micromol x L(-1). Curcumin exposure caused a significant increase in cellular GSH content rapidly as early as 3 h. Moreover, curcumin triggered the accumulation of Nrf2 in nucleus, and increased Nrf2 content in ARE complexes. These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.
Ye
She-fang
SF
Key Laboratory of Biomedical Engineering of Fujian, Medical College, Xiamen University, Xiamen 361005, China.
Hou
Zhen-qing
ZQ
Zhong
Li-ming
LM
Zhang
Qi-qing
QQ
D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D020218:Response Elements / Q000187:drug effects; D015398:Signal Transduction
D000970:Antineoplastic Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016660:NAD(P)H Dehydrogenase (Quinone); D005982:Glutathione Transferase; D005978:Glutathione; D003474:Curcumin