DOI QR코드

DOI QR Code

Effects of Benzyl Isothiocyanate and Its N-Acetylcysteine Conjugate on Induction of Detoxification Enzymes in Hepa1c1c7 Mouse Hepatoma Cells

  • Hwang, Eun-Sun (Department of Nutrition and Culinary Science and Korean Foods Global Center, Hankyong National University)
  • Received : 2014.08.08
  • Accepted : 2014.10.01
  • Published : 2014.12.31

Abstract

The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

References

  1. Fenwick GR, Heaney RK. 1983. Glucosinolates and their breakdown products in cruciferous crops, foods and feedingstuffs. Food Chem 11: 249-271. https://doi.org/10.1016/0308-8146(83)90074-2
  2. Lampe JW, Peterson S. 2002. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr 132: 2991-2994.
  3. Hwang ES, Jeffery EH. 2005. Induction of quinone reductase by the sulforaphane and N-acetylcysteine conjugate of sulforaphane in murine hepatoma cells. J Med Food 8: 198-203. https://doi.org/10.1089/jmf.2005.8.198
  4. Cramer JM, Jeffery EH. 2011. Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men. Nutr Cancer 63: 196-201. https://doi.org/10.1080/01635581.2011.523495
  5. Masuda H, Harada Y, Tanaka K, Nakajima M, Tateba H. 1996. Characteristic odorants of Wasabi, Japanese horseradish, in comparison with those of horseradish (Armoracia rusticana). In Biotechnology for Improved Foods and Flavors. ACS Symposium Series 637. American Chemical Society, Washington, DC, USA. p 67-78.
  6. Mennicke WH, Gorler K, Krumbiegel G. 1983. Metabolism of some naturally occurring isothiocyanates in the rat. Xenobiotica 13: 203-207. https://doi.org/10.3109/00498258309052256
  7. Conaway CC, Yang YM, Chung FL. 2002. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab 3: 233-255. https://doi.org/10.2174/1389200023337496
  8. Chung FL, Jiao D, Getahun SM, Yu MC. 1998. A urinary biomarker for uptake of dietary isothiocyanates in humans. Cancer Epidemiol Biomarkers Prev 7: 103-108.
  9. Hwang ES, Jeffery EH. 2003. Evaluation of urinary N-acetyl cysteinyl allyl isothiocyanate as a biomarker for intake and bioactivity of Brussels sprouts. Food Chem Toxicol 41: 1817-1825. https://doi.org/10.1016/S0278-6915(03)00235-7
  10. Kassie F, Laky B, Gminski R, Mersch-Sundermann V, Scharf G, Lhoste E, Kansmuller S. 2003. Effects of garden and water cress juices and their constituents, benzyl and phenethyl isothiocyanates, towards benzo(a)pyrene-induced DNA damage: a model study with the single cell gel electrophoresis/Hep G2 assay. Chem Biol Interact 142: 285-296. https://doi.org/10.1016/S0009-2797(02)00123-0
  11. Perocco P, Bronzetti G, Canistro D, Valgimigli L, Sapone A, Affatato A, Pedulli GF, Pozzetti L, Broccoli M, Iori R, Barillari J, Sblendorio V, Legator MS, Paolini M, Abdel-Rahman SZ. 2006. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver. Mutat Res 595: 125-136. https://doi.org/10.1016/j.mrfmmm.2005.11.007
  12. Wallig MA, Kingston S, Staack R, Jefferey EH. 1998. Induction of rat pancreatic glutathione S-transferase and quinone reductase activities by a mixture of glucosinolate breakdown derivatives found in brussels sprouts. Food Chem Toxicol 36: 365-373. https://doi.org/10.1016/S0278-6915(97)00156-7
  13. Steck SE, Gammon MD, Hebert JR, Wall DE, Zeisel SH. 2007. GSTM1, GSTT1, GSTP1, and GSTA1 polymorphisms and urinary isothiocyanate metabolites following broccoli consumption in humans. J Nutr 137: 904-909.
  14. Dinkova-Kostova AT, Talalay P. 2000. Persuasive evidence that quinone reductase type 1 (DT diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen. Free Radic Biol Med 29: 231-240. https://doi.org/10.1016/S0891-5849(00)00300-2
  15. Nioi P, Hayes JD. 2004. Contribution of NAD(P)H: quinone oxidoreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhydrocarbon receptor basic helix-loop-helix transcription factors. Mutat Res 555: 149-171. https://doi.org/10.1016/j.mrfmmm.2004.05.023
  16. Boone CW, Steele VE, Kelloff GJ. 1992. Screening for chemopreventive (anticarcinogenic) compounds in rodents. Mutat Res 267: 251-255. https://doi.org/10.1016/0027-5107(92)90069-E
  17. Song LL, Kosmeder JW 2nd, Lee SK, Gerhauser C, Lantvit D, Moon RC, Moriarty RM, Pezzuto JM. 1999. Cancer chemopreventive activity mediated by 4'-bromoflavone, a potent inducer of phase II detoxification enzyme. Cancer Res 59: 578-585.
  18. Sasaki JC, Fellers RS, Colvin ME. 2002. Metabolic oxidation of carcinogenic arylamines by P450 monooxygenases: theoretical support for the one-electron transfer mechanism. Mutat Res 506-507: 79-89. https://doi.org/10.1016/S0027-5107(02)00154-9
  19. Syed K, Doddapaneni H, Subramanian V, Lam YW, Yadav JS. 2010. Genome-to-function characterization of novel fungal P450 monooxygenases oxidizing polycyclic aromatic hydrocarbons (PAHs). Biochem Biophys Res Commun 399: 492-497. https://doi.org/10.1016/j.bbrc.2010.07.094
  20. Tan XL, Shi M, Tang H, Han W, Spivack SD. 2010. Candidate dietary phytochemicals modulate expression of phase II enzymes GSTP1 and NQO1 in human lung cells. J Nutr 140: 1404-1410. https://doi.org/10.3945/jn.110.121905
  21. Zhang Y, Tang L, Gonzalez V. 2003. Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol Cancer Ther 2: 1045-1052.
  22. Hwang ES, Lee HJ. 2006. Induction of quinone reductase by allylisothiocyanate (AITC) and the N-acetylcysteine conjugate of AITC in Hepa1c1c7 mouse hepatoma cells. Biofactors 26: 7-15. https://doi.org/10.1002/biof.5520260102
  23. Goosen TC, Mills DE, Hollenberg PF. 2001. Effects of benzyl isothiocyanate on rat and human cytochromes P450: identification of metabolites formed by P450 2B1. J Pharmacol Exp Ther 296: 198-206.
  24. Silverman RB. 1996. Mechanism-based enzyme inactivators. In Contemporary Enzyme Kinetics and Mechanisms. Purich DL, ed. Academic Press, San Diego, CA USA. p 291-335.

Cited by

  1. Poly(lactic-co-glycolic acid) nanoparticles for sustained release of allyl isothiocyanate: characterization, in vitro release and biological activity vol.34, pp.3, 2017, https://doi.org/10.1080/02652048.2017.1323037
  2. Bioavailability and metabolism of benzyl glucosinolate in humans consuming Indian cress (Tropaeolum majusL.) vol.60, pp.3, 2016, https://doi.org/10.1002/mnfr.201500633