The isothiocyanate sulforaphane induces the phase 2 response by signaling of the Keap1-Nrf2-are pathway: Implications for dietary protection against cancer

Dietary Modulation of Cell Signaling Pathways

Volumn , Issue , 2008, Pages 205-227

  Dinkova Kostova, Albena T ^a,b  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77958116145     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (109)

1. Talalay, P. et al., Biochemical studies on the mechanisms by which dietary antioxidants suppress mutagenic activity, Adv. Enzyme Regul., 17, 23, 1978.
2. Talalay, P., Chemoprotection against cancer by induction of phase 2 enzymes, Biofactors, 12, 5, 2000.
3. Kensler, T.W., Chemoprevention by inducers of carcinogen detoxication enzymes, Environ. Health Perspect., 105 (Suppl. 4), 965, 1997.
4. Dinkova-Kostova, A.T. and Talalay, P., 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, 2000.
5. Fahey, J.W. and Talalay, P., Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes, Food Chem. Toxicol., 37, 973, 1999.
6. Hayes, J.D. and McLellan, L.I., Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress, Free Radic. Res., 31, 273, 1999.
7. Wilkinson, J., IV, et al., Ferritin regulation by oxidants and chemopreventive xenobiotics, Adv. Enzyme Regul., 43, 135, 2003.
8. Kwak, M.K. et al., Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival, J. Biol. Chem., 278, 8135, 2003.
9. Anders, M.W., Glutathione-dependent bioactivation of haloalkanes and haloalkenes, Drug Metab. Rev., 36, 583, 2004.
10. De Long, M., Prochaska, H.J., and Talalay, P., Induction of NAD(P)H: quinone reductase in murine hepatoma cells by phenolic antioxidants, azo dyes, and other chemoprotectors: a model system for the study of anticarcinogens, Proc. Natl. Acad. Sci. USA, 83, 787, 1986.
11. Prochaska, H.J. and Santamaria, A.B., 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, 1988.
12. Prochaska, H.J., Santamaria, A.B., and Talalay, P., Rapid detection of inducers of enzymes that protect against carcinogens, Proc. Natl. Acad. Sci. USA, 89, 2394, 1992.
13. Fahey, J.W. et al., The “Prochaska” microtiter plate bioassay for inducers of NQO1, Methods Enzymol., 382, 243, 2004.
14. Zhang, Y. et al., A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure, Proc. Natl. Acad. Sci. USA, 89, 2399, 1992.
15. Fahey, J.W., Zhang, Y., and Talalay, P., Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. USA, 94, 10367, 1997.
16. Prestera, T. et al., The electrophile counterattack response: protection against neoplasia and toxicity, Adv. Enzyme Regul., 33, 281, 1993.
17. Dinkova-Kostova, A.T., Fahey, J.W., and Talalay, P., Chemical structures of inducers of nicotinamide quinone oxidoreductase 1 (NQO1), Methods Enzymol., 382, 423, 2004.
18. Dinkova-Kostova, A.T., Protection against cancer by plant phenylpropenoids: induction of mammalian anticarcinogenic enzymes, Mini Rev. Med. Chem., 2, 595, 2002.
19. Kang, Y.-H. and Pezzuto, J.M. Induction of quinone reductase as a primary screen for natural product anticarcinogens. Methods Enzymol., 382, 380, 2004.
20. Fahey, J.W., Zalcmann, A.T., and Talalay, P., The chemical diversity and distribution of glucosinolates and isothiocyanates among plants, Phytochemistry, 56, 5, 2001.
21. Halkier, B.A. and Gershenzon, J., Biology and biochemistry of glucosinolates, Annu. Rev. Plant Biol., 57, 303, 2006.
22. Robiquet, P.J. and Boutron, F., Sur la semence de moutarde, J. Pharm. Chim., 17, 279, 1831.
23. Wittstock, U. and Gershenzon, J., Constitutive plant toxins and their role in defense against herbivores and pathogens, Curr. Opin. Plant Biol., 5, 300, 2002.
24. Rask, L. et al., Myrosinase: gene family evolution and herbivore defense in Brassicaceae, Plant Mol. Biol., 42, 93, 2000.
25. Matusheski, N.V. and Jeffery, E.H., Comparison of the bioactivity of two glucoraphanin hydrolysis products found in broccoli, sulforaphane and sulforaphanenitrile, J. Agric. Food Chem., 49, 5743, 2001.
26. Wittstock, U. and Halkier, B.A., Glucosinolate research in the Arabidopsis era, Trends Plant Sci., 2002, 263, 2002.
27. Bones, A.M. and Rossiter, J.T., The enzymic and chemically induced decomposition of glucosinolates, Phytochemistry, 67, 1053, 2006.
28. Matusheski, N.V., Juvik, J.A., and Jeffery, E.H., Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli, Phytochemistry, 65, 1273, 2004.
29. Ratzka, A. et al., Disarming the mustard oil bomb, Proc. Natl. Acad. Sci. USA, 99, 11223, 2002.
30. Wittstock, U. et al., Successful herbivore attack due to metabolic diversion of a plant chemical defense, Proc. Natl. Acad. Sci. USA, 101, 4859, 2004.
31. Burow, M. et al., Comparative biochemical characterization of nitrile-forming proteins from plants and insects that alter myrosinase-catalysed hydrolysis of glucosinolates, FEBS J., 273, 2432, 2006.
32. Bridges, M. et al., Spatial organization of the glucosinolate-myrosinase system in brassica specialist aphids is similar to that of the host plant, Proc. Biol. Sci., 269, 187, 2002.
33. Müller, C. and Wittstock, U., Uptake and turn-over of glucosinolates sequestered in the sawfly Athalia rosae, Insect. Biochem. Mol. Biol., 35, 1189, 2005.
34. Bussy, A., Sur la formation de l’huile essentielle de moutarde, J. Pharm., 27, 464, 1840.
35. Björkman, R. and Lönnerdal, B., Studies on myrosinases. 3. Enzymatic properties of myrosinases from Sinapis alba and Brassica napus seeds, Biochim. Biophys. Acta., 327, 121, 1973.
36. Lönnerdal, B. and Janson, J.C., Studies on Brassica seed proteins. I. The low molecular weight proteins in rapeseed. Isolation and characterization, Biochim. Biophys. Acta., 278, 175, 1972.
37. Bones, A.M. and Slupphaug, G., Purification, characterization and partial amino acid sequencing of β-thioglucosidase from Brassica napus L., J. Plant Physiol., 134, 722, 1989.
38. Durham, P.L. and Poulton, J.E., Effect of castanospermine and related polyhydroxyalkaloids on purified myrosinase from Lepidium sativum seedlings, Plant Physiol., 90, 48, 1989.
39. Ohtsuru, M. and Hata, T., The interaction of L-ascorbic acid with the active center of myrosinase, Biochim. Biophys. Acta. 567, 384, 1979.
40. Li, X. and Kushad, M.M., Purification and characterization of myrosinase from horseradish (Armoracia rusticana) roots, Plant Physiol. Biochem., 43, 503, 2005.
41. Shikita, M. et al., An unusual case of “uncompetitive activation” by ascorbic acid: purification and kinetic properties of a myrosinase from Raphanus sativus seedlings, Biochem. J., 341, 725, 1999.
42. Burmeister, W.P. et al., The crystal structures of Sinapis alba myrosinase and a covalent glycosyl-enzyme intermediate provide insights into the substrate recognition and active-site machinery of an S-glycosidase, Structure, 5, 663, 1997.
43. Burmeister, W.P. et al., High resolution X-ray crystallography shows that ascorbate is a cofactor for myrosinase and substitutes for the function of the catalytic base, J. Biol. Chem., 275, 39385, 2000.
44. Shapiro T.A. et al., Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables, Cancer Epidemiol. Biomarkers Prev., 7, 1091, 1998.
45. Jiang, Z.-Q. et al., Differential responses from seven mammalian cell lines to the treatments of detoxifying enzyme inducers, Life Sci., 72, 2243, 2003.
46. Svehlikova, V. et al., Interactions between sulforaphane and apigenin in the induction of UGT1A1 and GSTA1 in CaCo-2 cells, Carcinogenesis, 25, 1629, 2004.
47. Fei, P. et al., Transcription regulation of rat glutathione S-transferase Ya subunit gene expression by chemopreventive agents, Pharm. Res., 13, 1043, 1996.
48. Zhang, J. et al., Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation, Carcinogenesis, 24, 497, 2003.
49. Mahéo, K. et al., Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes, Cancer Res., 57, 3649, 1997.
50. Morel, F. et al., The use of primary hepatocyte cultures for the evaluation of chemoprotective agents, Cell Biol. Toxicol., 13, 323, 1997.
51. Bao, Y., Bacon, J., and Williamson, G., Effect of phytochemicals on PhIP-DNA adduct formation in human Hep G2 and hepatocytes, in Biologically-Active Phytochemicals in Food, Pfannhauser, W., Fenwick, G.R., and Khokar, S., Eds., Royal Society of Chemistry, 2001, pp. 589-591.
52. Bacon, J.R. et al., Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes, Carcinogenesis, 24, 1903, 2003.
53. Brooks, J.D. and Paton, V.G., Potent induction of carcinogen defence enzymes with sulforaphane, a putative prostate cancer chemopreventive agent, Prostate Cancer Prostatic Dis., 2, S8, 1999.
54. Brooks, J.D., Paton, V.G., and Vidanes G., Potent induction of phase 2 enzymes in human prostate cells by sulforaphane, Cancer Epidemiol. Biomarkers Prev., 10, 949, 2001.
55. Munday, R. and Munday, C.M., Induction of phase II detoxification enzymes in rats by plant-derived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and related compounds, J. Agric. Food Chem., 52, 1867, 2004.
56. McMahon, M. et al., The Cap ʼn' Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes, Cancer Res., 61, 3299, 2001.
57. Thimmulappa, R.K. et al., Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray, Cancer Res., 62, 5196, 2002.
58. Hu, R. et al., In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat, J. Pharmacol. Exp., Ther., 310, 263, 2004.
59. Traka, M. et al., Transcriptome analysis of human colon Caco-2 cells exposed to sulforaphane, J. Nutr., 135, 1865, 2005.
60. Hu, R. et al., Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice, Cancer Lett., 243, 170, 2006.
61. Nguyen, T., Sherratt, P.J., and Pickett, C.B., Regulatory mechanisms controlling gene expression mediated by the antioxidant response element, Annu. Rev. Pharmacol. Toxicol., 43, 233, 2003.
62. Motohashi, H. and Yamamoto, M., Nrf2-Keap1 defines a physiologically important stress response mechanism, Trends Mol. Med., 10, 549, 2004.
63. Dinkova-Kostova, A.T., Holtzclaw, W.D., and Kensler, T.W., The role of Keap1 in cellular protective responses, Chem. Res. Toxicol., 18, 1779, 2005.
64. Kobayashi, M. and Yamamoto, M., Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species, Adv. Enzyme Regul., 46, 113, 2006.
65. Kensler, T.W., Wakabayashi, N., and Biswal, S., Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway, Annu. Rev. Pharmacol. Toxicol., 47, 89, 2007.
66. Li, X. et al., Crystal structure of the Kelch domain of human Keap1, J. Biol. Chem., 279, 54750, 2004.
67. Padmanabhan, B. et al., Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer, Mol. Cell., 21, 689, 2006.
68. Tong, K.I. et al., Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model, Mol. Cell. Biol., 26, 2887, 2006.
69. McMahon, M. et al., Dimerization of substrate adaptors can facilitate cullinmediated ubiquitylation of proteins by a “tethering” mechanism: a two-site interaction model for the Nrf2-Keap1 complex, J. Biol. Chem., 281, 24756, 2006.
70. Dinkova-Kostova, A.T., Holtzclaw, W.D., and Wakabayashi, N., Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein, Biochemistry, 44, 6889, 2005.
71. Dinkova-Kostova, A.T. et al., Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants, Proc. Natl. Acad. Sci. USA, 99, 11908, 2002.
72. Wakabayashi, N. et al., Protection against electrophile and oxidant stress by induction of the phase 2 response: fate of cysteines of the Keap1 sensor modified by inducers, Proc. Natl. Acad. Sci. USA, 101, 2040, 2004.
73. Hong, F., Freeman, M.L., and Liebler, D.C., Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane, Chem. Res. Toxicol., 18, 1917, 2005.
74. McMahon, M. et al., Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response elementdriven gene expression, J. Biol. Chem., 278, 21592, 2003.
75. Zhang, D.D. and Hannink, M., Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress, Mol. Cell Biol., 23, 8137, 2003.
76. Fahey, J.W. et al., Sulforaphane inhibits extracellular, intracellular, and anti bioticresistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors, Proc. Natl. Acad. Sci. USA, 99, 7610, 2002.
77. Xu, C. et al., Inhibition of 7,12-dimethylbenz(a)anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2, Cancer Res., 66, 8293, 2006.
78. Zhang, Y. et al., Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates, Proc. Natl. Acad. Sci. USA, 91, 3147, 1994.
79. Chung, F.L. et al., Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate, Carcinogenesis, 21, 2287, 2000.
80. Conaway, C.C. et al., Phenethyl isothiocyanate and sulforaphane and their N-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A/J mice, Cancer Res., 65, 8548, 2005.
81. Gills, J.J. et al., Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion, Cancer Lett., 236, 72, 2006.
82. Kuroiwa, Y. et al., Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters, Cancer Lett., 241, 275, 2006.
83. min mice, FASEB J., 20, 506, 2006.
84. Hu, R. et al., Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable, Carcinogenesis, 27, 2038, 2006.
85. Lu, Y.P. et al., Topical applications of caffeine or (-)-epigallocatechin gallate (EGCG) inhibit carcinogenesis and selectively increase apoptosis in UVB-induced skin tumors in mice, Proc. Natl. Acad. Sci. USA, 99, 12455, 2002.
86. Dinkova-Kostova, A.T. et al., Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts, Cancer Lett., 240, 243, 2006.
87. Gamet-Payrastre, L. et al., Signaling pathways and intracellular targets of sulforaphane mediating cell cycle arrest and apoptosis, Curr. Cancer Drug Targets, 6, 135, 2006.
88. Bertl, E., Bartlsch, H., and Gerhäuser, C., Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention, Mol. Cancer Ther., 5, 575, 2006.
89. Barcelo, S. et al., CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane, Carcinogenesis, 17, 277, 1996.
90. Heiss, E. et al., Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms, J. Biol. Chem., 276, 32008, 2001.
91. Myzak, M.C. et al., A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase, Cancer Res., 64, 5767, 2004.
92. Kolm, R.H. et al., Isothiocyanates as substrates for human glutathione transferases: structure-activity studies, Biochem. J., 311, 453, 1995.
93. Zhang, Y. et al., Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases, Biochem. Biophys. Res. Commun., 206, 748, 1995.
94. Joseph M.A. et al., Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk, Nutr. Cancer, 50, 206, 2004.
95. Lin, H.J. et al., Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas, Cancer Epidemiol. Biomarkers Prev., 7, 647, 1998.
96. Spitz, M.R. et al., Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk, Cancer Epidemiol. Biomarkers Prev., 9, 1017, 2000.
97. Wang, L.I. et al., Dietary intake of cruciferous vegetables, glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population. Cancer Causes Control, 15, 977, 2004.
98. Zhang, Y. et al., Spectroscopic quantitation of organic isothiocyanates by cyclocondensation with vicinal dithiols, Anal. Biochem., 205, 100, 1992.
99. Zhang, Y. et al., Quantitative determination of isothiocyanates, dithiocarbamates, carbon disulfide, and related thiocarbonyl compounds by cyclocondensation with 1,2-benzenedithiol. Anal. Biochem., 239, 160, 1996.
100. Shapiro, T.A. et al., Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans, Cancer Epidemiol. Biomarkers Prev., 10, 501, 2001.
101. Ye, L. and Zhang, Y., Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of phase 2 detoxification enzymes, Carcinogenesis, 22, 1987, 2001.
102. Zhang, Y., Molecular mechanism of rapid cellular accumulation of anticarcinogenic isothiocyanates, Carcinogenesis, 22, 425, 2001.
103. Ye, L. et al., Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans, Clin. Chim. Acta. 316, 43, 2002.
104. Kensler, T.W. et al., Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People’s Republic of China, Cancer Epidemiol. Biomarkers Prev., 14, 2605, 2005.
105. Shapiro, T.A. et al., Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical Phase I study, Nutr. Cancer, 55, 53, 2006.
106. Agarwal, S. et al., Simultaneous determination of sulforaphane and its major metabolites from biological matrices with liquid chromatography-tandem mass spectroscopy, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 840, 99, 2006.
107. Gasper, A.V. et al., Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli, Am. J. Clin. Nutr., 82, 1283, 2005.
108. Al-janobi, A. et al., Quantitative measurement of sulforaphane, iberin and their mercapturic acid pathway metabolites in human plasma and urine using liquid chromatography- tandem electrospray ionisation mass spectrometry, J. Chromatogr. B Analyt. Technol. Biomed. Life. Sci., 884, 223, 2006.
109. Mithen, R. et al., Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells, Theor. Appl. Genet., 106, 727, 2003.