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Archives of Toxicology

, Volume 86, Issue 10, pp 1505–1514 | Cite as

The naturally occurring aliphatic isothiocyanates sulforaphane and erucin are weak agonists but potent non-competitive antagonists of the aryl hydrocarbon receptor

  • Ahmad F. Abdull Razis
  • Natalya Hanlon
  • Ewa Soltys
  • Veronika Krizova
  • Renato Iori
  • Kathryn E. Plant
  • Nick Plant
  • Costas Ioannides
Molecular Toxicology

Abstract

As the Ah receptor target gene products play a critical role in chemical carcinogenesis, antagonists are considered as potential chemopreventive agents. It is demonstrated in this paper that the isothiocyanates R,S-sulforaphane and erucin are non-competitive antagonists of the aryl hydrocarbon (Ah) receptor. Both isothiocyanates were poor agonists for the receptor and elevated CYP1A1 mRNA levels only modestly when incubated with precision-cut rat liver slices. In contrast, the classical Ah receptor agonist benzo[a]pyrene was a potent inducer of CYP1A1 mRNA levels, with this effect being effectively antagonized by the two isothiocyanates. In further studies, it was demonstrated that R,S-sulforaphane could both prevent the interaction of and displace already bound benzo[a]pyrene from the Ah receptor, but no concentration dependency was observed with respect to the isothiocyanate. Both erucin and R,S-sulforaphane antagonized the benzo[a]pyrene-mediated increase in the CYP1A-mediated O-deethylation of ethoxyresorufin in rat precision-cut liver slices. Of the two isomers of R,S-sulforaphane, the naturally occurring R-isomer was more effective than the S-isomer in antagonizing the activation of the Ah receptor by benzo[a]pyrene. Antagonism of the Ah receptor may be a major contributor to the established chemoprevention of aliphatic isothiocyanates.

Keywords

Isothiocyanates Glucosinolates Chemoprevention Sulforaphane Erucin Ah receptor 

Notes

Acknowledgments

The authors thank the Malaysian Government for funding this work through a PhD award to one of them (AF Abdull Razis) and Drs M Denison (University of California, Davis, USA) and A Roda (University of Bologna, Italy) for the kind gift of the transfected H1L1. 1c2 cells.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ahmad F. Abdull Razis
    • 1
    • 3
  • Natalya Hanlon
    • 1
  • Ewa Soltys
    • 1
  • Veronika Krizova
    • 1
  • Renato Iori
    • 2
  • Kathryn E. Plant
    • 1
  • Nick Plant
    • 1
  • Costas Ioannides
    • 1
  1. 1.Molecular Toxicology Group, Faculty of Health and Medical SciencesUniversity of SurreyGuildford, SurreyUK
  2. 2.Agricultural Research Council—Industrial Crop Research Centre (CRA-CIN)BolognaItaly
  3. 3.Department of Food Science, Faculty of Food Science and TechnologyUniversiti Putra MalaysiaSerdangMalaysia

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