Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Sulforaphane is Superior to Glucoraphanin in Modulating Carcinogen-Metabolising Enzymes in Hep G2 Cells

  • Abdull Razis, Ahmad Faizal (Food Safety Research Centre (FOSREC), Faculty of Food Science and Technology, Universiti Putra Malaysia) ;
  • Noor, Noramaliza Mohd (Department of Imaging, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia)
  • Published : 2013.07.30
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Abstract

Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 ${\mu}M$) for 24 hours. Glucoraphanin at higher concentration (25 ${\mu}M$) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 ${\mu}M$. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen-metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.

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References

  1. Abdull Razis AF, Bagatta M, De Nicola GR, et al (2010). Intact glucosinolates modulate hepatic cytochrome P450 and phase II conjugation activities and may contribute directly to the chemopreventive activity of cruciferous vegetables. Toxicol, 277, 74-85. https://doi.org/10.1016/j.tox.2010.08.080
  2. Abdull Razis AF, Iori R, Ioannides C (2011). The natural chemopreventive phytochemical R-sulforaphane is a far more potent inducer of the carcinogen-detoxifying enzyme systems in rat liver and lung than the S-isomer. Int J Cancer, 128, 2775-82. https://doi.org/10.1002/ijc.25620
  3. Ambrosone CB, McCann SE, Freudenheim JL, et al (2004). Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J Nutr, 134, 1134-8.
  4. Anwar-Mohamed A, El-Kadi AOS (2009). Sulforaphane induces CYP1A1 mRNA, protein, and catalytic activity levels via an AhR-dependent pathway in murine hepatoma Hepa1c1c7 cells and HepG2 cells. Cancer Lett, 275, 93-101. https://doi.org/10.1016/j.canlet.2008.10.003
  5. Bradford MM (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding. Anal Biochem, 72, 248-54. https://doi.org/10.1016/0003-2697(76)90527-3
  6. Burke MD, Mayer RT (1974). Ethoxyresorufin; direct fluorimetric assay of a microsomal O-dealkylation which is preferentially inducible by 3-methylcholanthrene. Drug Metab Disp, 2, 583-8.
  7. Getahun SM, Chung F-L (1999). Conversion of isothiocyanates in humans after ingestion of cooked watercress. Cancer Epidemiol Biomark Prev, 8, 447-51.
  8. Habig WH, Pabst MJ, Jakoby WB (1974). Glutathione S-transferase, the first enzymic step in mercapturic acid formation. J Biol Chem, 249, 7130-9.
  9. Hanlon N, Coldham N, Gielbert A, et al (2009a). Repeated intake of broccoli does not lead to higher plasma levels of sulforaphane in human volunteers. Cancer Lett, 284, 15-20. https://doi.org/10.1016/j.canlet.2009.04.004
  10. Hanlon N, Coldham N, Sauer MJ, et al (2009b). Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane. Chem-Biol Inter, 177, 115-20. https://doi.org/10.1016/j.cbi.2008.08.015
  11. Hanlon N, Okpara M, Coldham N, et al (2008). Modulation of rat hepatic and pulmonary cytochromes P450 and phase II enzyme systems by erucin, an isothiocyanate structurally related to sulforaphane. J Agric Food Chem, 56, 7866-71. https://doi.org/10.1021/jf801456h
  12. Hecht SS (2000). Inhibition of carcinogenesis by isothiocyanates. Drug Met Rev, 32, 395-411. https://doi.org/10.1081/DMR-100102342
  13. Hintze KJ, Keck A-S, Finley JW, et al (2003). Induction of hepatic thioredoxin reductase activity by sulforaphane, both in Hepa1c1c7 cells and in male Fisher 344 rats. J Nutr Biochem, 14, 173-9. https://doi.org/10.1016/S0955-2863(02)00282-6
  14. 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
  15. Juge N, Mithen RF, Traka M (2007). Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci, 64, 1105-27. https://doi.org/10.1007/s00018-007-6484-5
  16. Kassie F, Laky B, Gminski R, et al (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/HepG2 assay. Chem-Biol Inter, 142, 285-96. https://doi.org/10.1016/S0009-2797(02)00123-0
  17. Kuroiwa Y, Nishikawa A, Kitamura Y, et al (2006). Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer Lett, 241, 275-80. https://doi.org/10.1016/j.canlet.2005.10.028
  18. Lam TK, Gallicchio L, Lindsley K, et al (2009). Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev, 18, 184-95. https://doi.org/10.1158/1055-9965.EPI-08-0710
  19. Papi A, Orlandi M, Bartolini G, et al (2008). Cytotoxic and antioxidant activit of 4-263 methylthio-3-butenyl isothiocyanate from Raphanus Sativus L. (Kaiware Daikon) sprouts. J Agric Food Chem, 56, 875-83. https://doi.org/10.1021/jf073123c
  20. Perocco P, Bronzetti G, Canistro D, et al (2006). Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolising enzymes and increases free radical generation in rat liver. Mut Res, 595, 125-36. https://doi.org/10.1016/j.mrfmmm.2005.11.007
  21. Prohaska HJ, Santamaria AB (1988). Direct measurement of NAD(P)H:quinone reductase from cells cultured in microtiter wells: a screening assay for anticarcinogenic enzyme inducers. Anal Biochem, 169, 328-36. https://doi.org/10.1016/0003-2697(88)90292-8
  22. Rudolf E, Cervinka M (2011). Sulforaphane induces cytotoxicity and lysosome- and mitochondria-dependent cell death in colon cancer cells with deleted p53. Toxicol in vitro, 25, 1302-9. https://doi.org/10.1016/j.tiv.2011.04.019
  23. Scholl C, Eshelman BD, Barnes DM, et al (2011). Raphasatin is a more potent inducer of the detoxification enzymes than its degradation products. J Food Sci, 76, 504-11.
  24. Sharma C, Sadrieh L, Priyani A, et al (2011). Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells. Cancer Epidemiol, 35, 272-8. https://doi.org/10.1016/j.canep.2010.09.008
  25. Verkerk R, Schreiner M, Krumbein A, et al (2009). Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health. Mol Nutr Food Res, 53, 219-65. https://doi.org/10.1002/mnfr.200800065
  26. Visentin M, Tava A, Iori R, et al (1992). Isolation and Identification of trans-4-(methylthio)-3-butenyl-glucosinolate from radish roots (Raphanus sativus L.). J Agric Food Chem, 40, 1687-91. https://doi.org/10.1021/jf00021a041
  27. Zhang Y (2004). Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action. Mutat Res, 555, 173-90. https://doi.org/10.1016/j.mrfmmm.2004.04.017

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