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

doi:10.5246/jcps.2016.08.062

Abstract

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 synergisticallyinduced 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.

Key words: Antioxidant response element, Curcumin, HepG2-C8 cells, HO-1, Nrf2, Sulforaphane, UGT1A1

CLC Number:

R962

Supporting:

Francisco Fuentes, Yury Gomez, Ximena Paredes-Gonzalez, Avantika Barve, Sujit Nair, Siwang Yu, Constance Lay Lay Saw, Ah-Ng Tony Kong. Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(8): 559-569.

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