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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
  • Contact: Tel.: +848-455-6369, Fax: +732-455-3134, E-mail: KongT@pharmacy.rutgers.edu
  • 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).

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

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