Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (8): 559-569.DOI: 10.5246/jcps.2016.08.062

• Cancer prevention by traditional Chinese medicine and plant phytochemicals column •     Next Articles

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

Francisco Fuentes1#, Yury Gomez2#, Ximena Paredes-Gonzalez2, Avantika Barve3, Sujit Nair4, Siwang Yu5, Constance Lay Lay Saw2, Ah-Ng Tony Kong2*   

  1. 1. Facultad de Agronomía e Ingeniería Forestal, Pontificia Universidad Católica de Chile, Casilla 306-22, Santiago, Chile
    2. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, New Jersey 08854, USA
    3. Novartis Institutes for Biomedical Research, East Hanover, NJ-07470, USA
    4. Amrita Cancer Discovery Biology Laboratory, Amrita Vishwa Vidyapeetham University, Amritapuri, Clappana P.O., Kollam, Kerala-690525, India
    5. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2016-03-15 Revised:2016-04-10 Online:2016-09-01 Published:2016-04-24
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  • Supported by:

    Part by Institutional Funds and by R01-CA118947, R01-CA152826, from the National Cancer Institute (NCI), R01-AT007065 from the National Center for Complementary and Alternative Medicines (NCCAM) and the Office of Dietary Supplements (ODS).


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

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