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Naturally-Occurring Glucosinolates, Glucoraphanin and Glucoerucin, are Antagonists to Aryl Hydrocarbon Receptor as Their Chemopreventive Potency

  • Published : 2015.09.02

Abstract

As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several pathophysiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

References

  1. Abdull Razis AF, Mohd Noor (2013). Cruciferous vegetables: dietary phytochemicals for cancer prevention. Asian Pac J Cancer Prev, 14, 1565-70. https://doi.org/10.7314/APJCP.2013.14.3.1565
  2. Amakura Y, Yoshimura M, Takaoka M, et al (2014). Characterization of natural aryl hydrocarbon receptor agonists from cassia seed and rosemary. Molecules, 19, 4956-66. https://doi.org/10.3390/molecules19044956
  3. Barouki R, Coumoul X, Fernandez-Salguero PM (2007) The aryl hydrocarbon receptor, more than a xenobiotic-interacting protein. FEBS Lett, 581, 3608-15. https://doi.org/10.1016/j.febslet.2007.03.046
  4. Bheemreddy RM, Jeffery EH. (2007). The metabolic fate of purified glucoraphanin in F344 rats. J Agric Food Chem, 55, 2861-66. https://doi.org/10.1021/jf0633544
  5. Cho H-J, Yoon I-S. (2015). Pharmacokinetic interactions of herbs with cytochrome P450 and P-Glycoprotein. Evid Based Complementary Altern Med.
  6. Chun J-H, Arasu MV, Lim Y-P, et al (2013). Variation of major glucosinolates in different varieties and lines of rocket salad. Hortic Environ Biotechnol, 54, 206-13. https://doi.org/10.1007/s13580-013-0122-y
  7. Cwik MJ, Wu H, Muzzio M, et al (2010). Direct quantitation of glucoraphanin in dog and rat plasma by LC-MS/MS. J Pharmaceut Biomed Analysis, 52, 544-9. https://doi.org/10.1016/j.jpba.2010.01.020
  8. EEC Regulation 1864/90, 1990. Enclosure VIII. Off. J Eur Commun. 170, 27-34.
  9. Hanieh H (2014). Toward understanding the role of aryl hydrocarbon receptor in the immune system: current progress and future trends. Biomed Res Int.
  10. Hecht SS. (2000). Inhibition of carcinogenesis by isothiocyanates. Drug Met Rev, 32, 395-411. https://doi.org/10.1081/DMR-100102342
  11. Ioannides C, Lewis DF. (2004). Cytochrome P450 in the bioactivation of chemicals. Curr Top Med Chem, 4, 1767-88. https://doi.org/10.2174/1568026043387188
  12. Lu YF, Santostefano M, Cunningham BD, et al (1995). Identification of 3'-methoxy-4'-nitroflavone as a pure aryl hydrocarbon (Ah) receptor antagonist and evidence for more than one form of the nuclear Ah receptor in MCF-7 human breast cancer cells. Arch Biochem Biophys, 316, 470-7. https://doi.org/10.1006/abbi.1995.1062
  13. Murray IA, Flaveny CA, DiNatale BC, et al (2010). Antagonism of aryl hydrocarbon receptor signalling by 6,2'-4'-trimethoxyflavone. J Pharmacol Exptl Ther, 332, 135-44. https://doi.org/10.1124/jpet.109.158261
  14. Nakamura Y, Miyoshi M (2010). Electrophiles in food; the current status of isothiocyanates and their chemical biology. Biosci Biotechnol Biosc, 74, 242-5. https://doi.org/10.1271/bbb.90731
  15. Okino ST, Pookot D, Basak S. et al (2009). Toxic and Chemopreventive Ligands Preferentially Activate Distinct Aryl Hydrocarbon Receptor Pathways: Implications for Cancer Prevention. Cancer Prev Res, 2, 251-6. https://doi.org/10.1158/1940-6207.CAPR-08-0146
  16. Pushparajah DS, Umachandran M, Nazir T, et al (2008). Upregulation of CYP1A/B in rat lung and liver, and human precision-cut slices by a series of polycyclic aromatic hydrocarbons; association with the Ah locus and importance of molecular size. Toxicol In Vitro, 22, 128-45. https://doi.org/10.1016/j.tiv.2007.08.014
  17. Safe S. (2001). Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett, 120, 1-7. https://doi.org/10.1016/S0378-4274(01)00301-0
  18. Shi S, Yoon DY, Hodge-Bell KC, et al (2009). The aryl hydrocarbon receptor nuclear translocator (Arnt) is required for tumor initiation by benzo[a]pyrene. Carcinogenesis, 30, 1957-61. https://doi.org/10.1093/carcin/bgp201
  19. Shimizu Y, Nakatsuru Y, Ichinose M, et al (2000). Benzo[a] pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci USA, 97, 779-82. https://doi.org/10.1073/pnas.97.2.779
  20. Tsay JJ, Tchou-Wong KM, Greenberg AK, et al (2013). Aryl hydrocarbon receptor and lung cancer. Anticancer Res, 33, 1247-56.
  21. Visentin M, Tava A, Iori R, Palmieri S. (1992). Isolation and Identification of trans-4-(methylthio)-3-butenylglucosinolate from radish roots (Raphanus sativus L.). J Agric Food Chem, 40, 1687-91. https://doi.org/10.1021/jf00021a041
  22. Wagner AE, Ernst I, Iori R, et al (2010). Sulforaphane but not ascorbigen, indole-3-carbinole and ascorbic acid activates the transcription factor Nrf2 and induces phase-2 and antioxidant enzymes in human keratinocytes in culture. Exp Dermatol, 19, 137-44. https://doi.org/10.1111/j.1600-0625.2009.00928.x
  23. Wang H, Griffiths S, Williamson G. (1997). Effect of glucosinolate breakdown products on ${\beta}$-naphthoflavoneinduced expression of human cytochrome P450 1Al via the Ah receptor in Hep G2 cells. Cancer Lett, 114, 121-5. https://doi.org/10.1016/S0304-3835(97)04640-5
  24. Whitlock JP, Jr (1999). Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol, 39, 103-25. https://doi.org/10.1146/annurev.pharmtox.39.1.103
  25. Wohak LE, Krais AM, Kucab JE, et al (2014). Carcinogenic polycyclic aromatic hydrocarbons induce CYP1A1 in human cells via a p53 dependent mechanism. Arch Toxicol.

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