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The dietary phytochemicals curcumin (CUR) and sulforaphane (SFN) have shown remarkable cancer chemopreventiveeffects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes bycombining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE (antioxidant response element) responsein HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhancethe induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFNor both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes–heme oxygenase-1 (HO-1) andUDP-glucuronosyltransferase-1A (UGT1A)–was measured by real-time RT-PCR and western blotting. ARE-luciferase activitywas also quantified. Low doses of CUR (10 μM) and SFN (12.5 μM) significantly induced the expression of HO-1 and UGT1A1proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown toaffect 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 augmenttherapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partlyexplain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combininglow doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.
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 bycombining doses of CUR and SFN and the effect of their combination on the 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, SFNor 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. Low doses of CUR (10 μM) and SFN (12.5 μM) significantly induced the expression of HO-1 and UGT1A1proteins. Through the use of chemical inhibitors of mRNA and 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-C8cells. 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 express the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combininglow doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.