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Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane

Publication Type : Journal Article

Publisher : Journal of Chinese Pharmaceutical Sciences.

Source : Journal of Chinese Pharmaceutical Sciences, Volume 25, Number 8, p.559-569 (2016)

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Year : 2016

Abstract : The dietary phytochemicals curcumin (CUR) and sulforaphane (SFN) have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE (antioxidant response element) response in HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes-heme oxygenase-1 (HO-1) and UDP-glucuronosyltransferase-1A (UGT1A)-was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR (10 μM) and SFN (12.5 μM) significantly induced the expression of HO-1 and UGT1A1 proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in HepG2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans. © 2016 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University.

Cite this Research Publication : Fa Fuentes, Gomez, Yb, Paredes-Gonzalez, Xb, Barve, Ac, Nair, Sd, Yu, Se, Saw, C. L. Lb, and Kong, A. - N. Tb, “Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane”, Journal of Chinese Pharmaceutical Sciences, vol. 25, pp. 559-569, 2016.

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