Phytochemistry Reviews

, Volume 8, Issue 1, pp 269–282 | Cite as

Glucosinolates, isothiocyanates and human health

  • Maria TrakaEmail author
  • Richard Mithen


Concurrent with the increase in our knowledge of the genetic and environmental factors that lead to glucosinolate accumulation in plants, and the role of these compounds and their derivatives in mediating plant–herbivore interactions, there has been significant advances in our understanding of how glucosinolates and their products may contribute to a reduction in risk of carcinogenesis and heart disease when consumed as part of the diet. In this paper, we review the epidemiological evidence for the health promoting effects of cruciferous vegetables, the processes by which glucosinolates and isothiocyanates are absorbed and metabolised by humans, with particular regard to the role of glutathione S-transferases, and the biological activity of isothiocyanates towards mammalian cells and tissues.


Brassica Cancer Epidemiology GST Intervention studies 



Allyl ITC


Benzyl ITC


Cyclin-dependent kinase


Cyclooxygenase 2


Cytochrome P450






Glutathione S-transferase


Heme oxygenase 1


Inducible nitric oxide synthase




Kelch-like ECH-associated protein 1


Multidrug resistance associated protein




NAD(P)H:Quinone Oxidoreductase


Nuclear factor erythroid-derived 2-like 2


Phenylethyl ITC


Reactive oxygen species




Thioredoxin reductase 1


  1. 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 134:1134–1138PubMedGoogle Scholar
  2. Asakage M, Tsuno NH, Kitayama J et al (2006) Sulforaphane induces inhibition of human umbilical vein endothelial cells proliferation by apoptosis. Angiogenesis 9:83–91PubMedCrossRefGoogle Scholar
  3. Barcelo S, Gardiner JM, Gescher A et al (1996) CYP2E1-mediated mechanism of anti-genotoxicity of the broccoli constituent sulforaphane. Carcinogenesis 17:277–282PubMedCrossRefGoogle Scholar
  4. Basten GP, Bao Y, Williamson G (2002) Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells. Carcinogenesis 23:1399–1404PubMedCrossRefGoogle Scholar
  5. Bertl E, Bartsch H, Gerhauser C (2006) Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol Cancer Ther 5:575–585PubMedCrossRefGoogle Scholar
  6. Bogaards JJ, Verhagen H, Willems MI et al (1994) Consumption of Brussels sprouts results in elevated alpha-class glutathione S-transferase levels in human blood plasma. Carcinogenesis 15:1073–1075PubMedCrossRefGoogle Scholar
  7. Bonnesen C, Eggleston IM, Hayes JD (2001) Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer Res 61:6120–6130PubMedGoogle Scholar
  8. Brooks JD, Paton VG, Vidanes G (2001) Potent induction of phase 2 enzymes in human prostate cells by sulforaphane. Cancer Epidemiol Biomarkers Prev 10:949–954PubMedGoogle Scholar
  9. Brusewitz G, Cameron BD, Chasseaud LF et al (1977) The metabolism of benzyl isothiocyanate and its cysteine conjugate. Biochem J 162:99–107PubMedGoogle Scholar
  10. Carlson DG, Daxenbichler ME, Tookey HL et al (1987a) Glucosinolates in turnip tops and roots—cultivars grown for greens and or roots. J Am Soc Hortic Sci 112:179–183Google Scholar
  11. Carlson DG, Daxenbichler ME, Vanetten CH et al (1987b) Glucosinolates in crucifer vegetables—broccoli, brussels- sprouts, cauliflower, collards, kale, mustard greens, and kohlrabi. J Am Soc Hortic Sci 112:173–178Google Scholar
  12. Cheng DL, Hashimoto K, Uda Y (2004) In vitro digestion of sinigrin and glucotropaeolin by single strains of Bifidobacterium and identification of the digestive products. Food Chem Toxicol 42:351–357PubMedCrossRefGoogle Scholar
  13. Chiao JW, Chung FL, Kancherla R et al (2002) Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int J Oncol 20:631–636PubMedGoogle Scholar
  14. Chiao JW, Wu H, Ramaswamy G et al (2004) Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis 25:1403–1408PubMedCrossRefGoogle Scholar
  15. Chung FL, Jiao D, Getahun SM et al (1998) A urinary biomarker for uptake of dietary isothiocyanates in humans. Cancer Epidemiol Biomarkers Prev 7:103–108PubMedGoogle Scholar
  16. Chung FL, Conaway CC, Rao CV et al (2000) Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis 21:2287–2291PubMedCrossRefGoogle Scholar
  17. Cohen JH, Kristal AR, Stanford JL (2000) Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 92:61–68PubMedCrossRefGoogle Scholar
  18. Conaway CC, Getahun SM, Liebes LL et al (2000) Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer 38:168–178PubMedCrossRefGoogle Scholar
  19. Conaway CC, Wang CX, Pittman B et al (2005) 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 65:8548–8557PubMedCrossRefGoogle Scholar
  20. Cornelis MC, El-Sohemy A, Campos H (2007) GSTT1 genotype modifies the association between cruciferous vegetable intake and the risk of myocardial infarction. Am J Clin Nutr 86:752–758PubMedGoogle Scholar
  21. Cotton SC, Sharp L, Little J et al (2000) Glutathione S-transferase polymorphisms and colorectal cancer: a HuGE review. Am J Epidemiol 151:7–32PubMedGoogle Scholar
  22. Dahl EL, Mulcahy RT (2001) Cell-type specific differences in glutamate cysteine ligase transcriptional regulation demonstrate independent subunit control. Toxicol Sci 61:265–272PubMedCrossRefGoogle Scholar
  23. Dey M, Ribnicky D, Kurmukov AG et al (2006) In vitro and in vivo anti-inflammatory activity of a seed preparation containing phenethylisothiocyanate. J Pharmacol Exp Ther 317:326–333PubMedCrossRefGoogle Scholar
  24. Dickinson DA, Levonen AL, Moellering DR et al (2004) Human glutamate cysteine ligase gene regulation through the electrophile response element. Free Radic Biol Med 37:1152–1159PubMedCrossRefGoogle Scholar
  25. Dinkova-Kostova AT, Holtzclaw WD, Cole RN et al (2002) 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 99:11908–11913PubMedCrossRefGoogle Scholar
  26. Dinkova-Kostova AT, Fahey JW, Wade KL et al (2007) Induction of the phase 2 response in mouse and human skin by sulforaphane-containing broccoli sprout extracts. Cancer Epidemiol Biomarkers Prev 16:847–851PubMedCrossRefGoogle Scholar
  27. Elfoul L, Rabot S, Khelifa N et al (2001) Formation of allyl isothiocyanate from sinigrin in the digestive tract of rats monoassociated with a human colonic strain of Bacteroides thetaiotaomicron. FEMS Microbiol Lett 197:99–103PubMedCrossRefGoogle Scholar
  28. Fahey JW, Zalcmann AT, Talalay P (2001) The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 56:5–51PubMedCrossRefGoogle Scholar
  29. Fahey JW, Haristoy X, Dolan PM et al (2002) Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci USA 99:7610–7615PubMedCrossRefGoogle Scholar
  30. Faulkner K, Mithen R, Williamson G (1998) Selective increase of the potential anticarcinogen 4-methylsulphinylbutyl glucosinolate in broccoli. Carcinogenesis 19:605–609PubMedCrossRefGoogle Scholar
  31. Fimognari C, Nusse M, Cesari R et al (2002) Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane. Carcinogenesis 23:581–586PubMedCrossRefGoogle Scholar
  32. Fowke JH, Chung FL, Jin F et al (2003) Urinary isothiocyanate levels, brassica, and human breast cancer. Cancer Res 63:3980–3986PubMedGoogle Scholar
  33. Galan MV, Kishan AA, Silverman AL (2004) Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report. Dig Dis Sci 49:1088–1090PubMedCrossRefGoogle Scholar
  34. Gamet-Payrastre L, Li P, Lumeau S et al (2000) Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res 60:1426–1433PubMedGoogle Scholar
  35. Gasper AV, Al-Janobi A, Smith JA et al (2005) Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr 82:1283–1291PubMedGoogle Scholar
  36. Gasper AV, Traka M, Bacon JR et al (2007) Consuming broccoli does not induce genes associated with xenobiotic metabolism and cell cycle control in human gastric mucosa. J Nutr 137:1718–1724PubMedGoogle Scholar
  37. Gerhauser C, You M, Liu J et al (1997) Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes. Cancer Res 57:272–278PubMedGoogle Scholar
  38. Getahun SM, Chung FL (1999) Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress. Cancer Epidemiol Biomarkers Prev 8:447–451PubMedGoogle Scholar
  39. Gingras D, Gendron M, Boivin D et al (2004) Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary anticarcinogen from Brassica vegetables. Cancer Lett 203:35–43PubMedCrossRefGoogle Scholar
  40. Giovannucci E, Rimm EB, Liu Y et al (2003) A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev 12:1403–1409PubMedGoogle Scholar
  41. Hansson LE, Nyren O, Bergström R et al (1993) Diet and risk of gastric cancer. A population-based case–control study in Sweden. Int J Cancer 55:181–189PubMedCrossRefGoogle Scholar
  42. Haristoy X, Angioi-Duprez K, Duprez A et al (2003) Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice. Antimicrob Agents Chemother 47:3982–3984PubMedCrossRefGoogle Scholar
  43. Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61:154–166PubMedCrossRefGoogle Scholar
  44. Hayes JD, Flanagan JU, Jowsey IR (2005) Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88PubMedCrossRefGoogle Scholar
  45. Heidel AJ, Clauss MJ, Kroymann J et al (2006) Natural variation in MAM within and between populations of Arabidopsis lyrata determines glucosinolate phenotype. Genetics 173:1629–1636PubMedCrossRefGoogle Scholar
  46. Heiss E, Herhaus C, Klimo K et al (2001) Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem 276:32008–32015PubMedCrossRefGoogle Scholar
  47. Hill CB, Williams PH, Carlson DG et al (1987) Variation in glucosinolates in oriental Brassica vegetables. J Am Soc Hortic Sci 112:309–313Google Scholar
  48. Hong F, Freeman ML, Liebler DC (2005) Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem Res Toxicol 18:1917–1926PubMedCrossRefGoogle Scholar
  49. Hu R, Kim BR, Chen C et al (2003) The roles of JNK and apoptotic signaling pathways in PEITC-mediated responses in human HT-29 colon adenocarcinoma cells. Carcinogenesis 24:1361–1367PubMedCrossRefGoogle Scholar
  50. Hu R, Khor TO, Shen G et al (2006) Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable. Carcinogenesis 27:2038–2046PubMedCrossRefGoogle Scholar
  51. Huang C, Ma WY, Li J et al (1998) Essential role of p53 in phenethyl isothiocyanate-induced apoptosis. Cancer Res 58:4102–4106PubMedGoogle Scholar
  52. Itoh K, Tong KI, Yamamoto M (2004) Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic Biol Med 36:1208–1213PubMedCrossRefGoogle Scholar
  53. Itoh K, Wakabayashi N, Katoh Y et al (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13:76–86PubMedCrossRefGoogle Scholar
  54. Jackson SJ, Singletary KW (2004a) Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr 134:2229–2236PubMedGoogle Scholar
  55. Jackson SJ, Singletary KW (2004b) Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis 25:219–227PubMedCrossRefGoogle Scholar
  56. Jackson SJ, Singletary KW, Venema RC (2006) Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Vascul Pharmacol 46:77–84PubMedCrossRefGoogle Scholar
  57. Jeffery EH, Araya M (2008) Broccoli and health: a growing benefit. Phytochemistry ReviewsGoogle Scholar
  58. Jiang ZQ, Chen C, Yang B et al (2003) Differential responses from seven mammalian cell lines to the treatments of detoxifying enzyme inducers. Life Sci 72:2243–2253PubMedCrossRefGoogle Scholar
  59. Joseph MA, Moysich KB, Freudenheim JL et al (2004) Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer 50:206–213PubMedCrossRefGoogle Scholar
  60. Juge N, Mithen RF, Traka M (2007) Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci 64:1105–1127PubMedCrossRefGoogle Scholar
  61. Karmakar S, Weinberg MS, Banik NL et al (2006) Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience 141:1265–1280PubMedCrossRefGoogle Scholar
  62. Kensler TW, Chen JG, Egner PA et al (2005) 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 14:2605–2613PubMedCrossRefGoogle Scholar
  63. Khor TO, Keum YS, Lin W et al (2006) Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res 66:613–621PubMedCrossRefGoogle Scholar
  64. Khor TO, Cheung WK, Prawan A et al (2007) Chemoprevention of familial adenomatous polyposis in Apc(Min/+) mice by phenethyl isothiocyanate (PEITC). Mol CarcinogGoogle Scholar
  65. Kirsh VA, Peters U, Mayne ST et al (2007) Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst 99:1200–1209PubMedCrossRefGoogle Scholar
  66. Kliebenstein DJ, Gershenzon J, Mitchell-Olds T (2001) Comparative quantitative trait loci mapping of aliphatic, indolic and benzylic glucosinolate production in Arabidopsis thaliana leaves and seeds. Genetics 159:359–370PubMedGoogle Scholar
  67. Kolm RH, Danielson UH, Zhang Y et al (1995) Isothiocyanates as substrates for human glutathione transferases: structure-activity studies. Biochem J 311:453–459PubMedGoogle Scholar
  68. Kroymann J, Textor S, Tokuhisa JG et al (2001) A gene controlling variation in arabidopsis glucosinolate composition is part of the methionine chain elongation pathway. Plant Physiol 127:1077–1088PubMedCrossRefGoogle Scholar
  69. Kushad MM, Brown AF, Kurilich AC et al (1999) Variation of glucosinolates in vegetable crops of Brassica oleracea. J Agric Food Chem 47:1541–1548PubMedCrossRefGoogle Scholar
  70. Lin HJ, Probst-Hensch NM, Louie AD et al (1998) Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 7:647–652PubMedGoogle Scholar
  71. London SJ, Yuan JM, Chung FL et al (2000) Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China. Lancet 356:724–729PubMedCrossRefGoogle Scholar
  72. Lopez-Berenguer C, Carvajal M, Moreno DA et al (2007) Effects of microwave cooking conditions on bioactive compounds present in broccoli inflorescences. J Agric Food Chem 55:10001–10007PubMedCrossRefGoogle Scholar
  73. Maheo K, Morel F, Langouet S et al (1997) Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes. Cancer Res 57:3649–3652PubMedGoogle Scholar
  74. Matusheski NV, Jeffery EH (2001) Comparison of the bioactivity of two glucoraphanin hydrolysis products found in broccoli, sulforaphane and sulforaphane nitrile. J Agric Food Chem 49:5743–5749PubMedCrossRefGoogle Scholar
  75. Matusheski NV, Juvik JA, Jeffery EH (2004) Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli. Phytochemistry 65:1273–1281PubMedCrossRefGoogle Scholar
  76. McMahon M, Itoh K, Yamamoto M et al (2003) Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem 278:21592–21600PubMedCrossRefGoogle Scholar
  77. McWalter GK, Higgins LG, McLellan LI et al (2004) Transcription factor Nrf2 is essential for induction of NAD(P) H:quinone oxidoreductase 1, glutathione S-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. J Nutr 134:3499S–3506SPubMedGoogle Scholar
  78. Meyer DJ, Crease DJ, Ketterer B (1995) Forward and reverse catalysis and product sequestration by human glutathione S-transferases in the reaction of GSH with dietary aralkyl isothiocyanates. Biochem J 306:565–569PubMedGoogle Scholar
  79. Mithen R, Faulkner K, Magrath R et al (2003) Development of isothiocyanate-enriched broccoli, and its enhanced ability to induce phase 2 detoxification enzymes in mammalian cells. Theor Appl Genet 106:727–734PubMedGoogle Scholar
  80. Moseley PL (1997) Heat shock proteins and heat adaptation of the whole organism. J Appl Physiol 83:1413–1417PubMedGoogle Scholar
  81. Motohashi H, Katsuoka F, Engel JD et al (2004) Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1-Nrf2 regulatory pathway. Proc Natl Acad Sci U S A 101:6379–6384PubMedCrossRefGoogle Scholar
  82. Musk SR, Smith TK, Johnson IT (1995) On the cytotoxicity and genotoxicity of allyl and phenethyl isothiocyanates and their parent glucosinolates sinigrin and gluconasturtiin. Mutat Res 348:19–23PubMedCrossRefGoogle Scholar
  83. Myzak MC, Karplus PA, Chung FL et al (2004) A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res 64:5767–5774PubMedCrossRefGoogle Scholar
  84. Myzak MC, Hardin K, Wang R et al (2006) Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis 27:811–819PubMedCrossRefGoogle Scholar
  85. Nguyen T, Huang HC, Pickett CB (2000) Transcriptional regulation of the antioxidant response element. activation by Nrf2 and repression by MafK. J Biol Chem 275:15466–15473PubMedCrossRefGoogle Scholar
  86. Palop ML, Smiths JP, Tenbrink B (1995) Degradation of sinigrin by Lactobacillus-Agilis Strain R16. Int J Food Microbiol 26:219–229CrossRefGoogle Scholar
  87. Parnaud G, Li P, Cassar G et al (2004) Mechanism of sulforaphane-induced cell cycle arrest and apoptosis in human colon cancer cells. Nutr Cancer 48:198–206PubMedCrossRefGoogle Scholar
  88. Patten EJ, DeLong MJ (1999) Temporal effects of the detoxification enzyme inducer, benzyl isothiocyanate: activation of c-Jun N-terminal kinase prior to the transcription factors AP-1 and NFkappaB. Biochem Biophys Res Commun 257:149–155PubMedCrossRefGoogle Scholar
  89. Rabot S, Nugon-Baudon L, Raibaud P et al (1993) Rape-seed meal toxicity in gnotobiotic rats: influence of a whole human faecal flora or single human strains of Escherichia coli and Bacteroides vulgatus. Br J Nutr 70:323–331PubMedCrossRefGoogle Scholar
  90. Rose P, Faulkner K, Williamson G et al (2000) 7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes. Carcinogenesis 21:1983–1988PubMedCrossRefGoogle Scholar
  91. Rose P, Won YK, Ong CN et al (2005) Beta-phenylethyl and 8-methylsulphinyloctyl isothiocyanates, constituents of watercress, suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages. Nitric Oxide 12:237–243PubMedCrossRefGoogle Scholar
  92. Rouzaud G, Young SA, Duncan AJ (2004) Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Cancer Epidemiol Biomarkers Prev 13:125–131PubMedCrossRefGoogle Scholar
  93. Sarikamis G, Marquez J, MacCormack R et al (2006) High glucosinolate broccoli: a delivery system for sulforaphane. Molecular Breeding 18:219–228CrossRefGoogle Scholar
  94. Seow A, Shi CY, Chung FL et al (1998) Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes. Cancer Epidemiol Biomarkers Prev 7:775–781PubMedGoogle Scholar
  95. Seow A, Yuan JM, Sun CL et al (2002) Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study. Carcinogenesis 23:2055–2061PubMedCrossRefGoogle Scholar
  96. Shapiro TA, Fahey JW, Wade KL et al (1998) Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev 7:1091–1100PubMedGoogle Scholar
  97. Shen G, Khor TO, Hu R et al (2007) Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in ApcMin/+ mouse. Cancer Res 67:9937–9944PubMedCrossRefGoogle Scholar
  98. Singh AV, Xiao D, Lew KL et al (2004a) Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis 25:83–90PubMedCrossRefGoogle Scholar
  99. Singh SV, Herman-Antosiewicz A, Singh AV et al (2004b) Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J Biol Chem 279:25813–25822PubMedCrossRefGoogle Scholar
  100. Smith TK, Lund EK, Parker ML et al (2004) Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells. Carcinogenesis 25:1409–1415PubMedCrossRefGoogle Scholar
  101. Sønderby IE, Hansen BG, Bjarnholt N et al (2007) A systems biology approach identifies a R2R3 MYB gene subfamily with distinct and overlapping functions in regulation of aliphatic glucosinolates. PLoS ONE 2:e1322PubMedCrossRefGoogle Scholar
  102. Spitz MR, Duphorne CM, Detry MA et al (2000) Dietary intake of isothiocyanates: evidence of a joint effect with glutathione S-transferase polymorphisms in lung cancer risk. Cancer Epidemiol Biomarkers Prev 9:1017–1020PubMedGoogle Scholar
  103. Staack R, Kingston S, Wallig MA et al (1998) A comparison of the individual and collective effects of four glucosinolate breakdown products from brussels sprouts on induction of detoxification enzymes. Toxicol Appl Pharmacol 149:17–23PubMedCrossRefGoogle Scholar
  104. Steck SE, Gammon MD, Hebert JR et al (2007) GSTM1, GSTT1, GSTP1, and GSTA1 polymorphisms and urinary isothiocyanate metabolites following broccoli consumption in humans. J Nutr 137:904–909PubMedGoogle Scholar
  105. Sugie S, Okamoto K, Okumura A et al (1994) Inhibitory effects of benzyl thiocyanate and benzyl isothiocyanate on methylazoxymethanol acetate-induced intestinal carcinogenesis in rats. Carcinogenesis 15:1555–1560PubMedCrossRefGoogle Scholar
  106. Tang L, Zhang Y (2004) Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. J Nutr 134:2004–2010PubMedGoogle Scholar
  107. Tang L, Zhang Y (2005) Mitochondria are the primary target in isothiocyanate-induced apoptosis in human bladder cancer cells. Mol Cancer Ther 4:1250–1259PubMedCrossRefGoogle Scholar
  108. Tang L, Li G, Song L et al (2006) The principal urinary metabolites of dietary isothiocyanates, N-acetylcysteine conjugates, elicit the same anti-proliferative response as their parent compounds in human bladder cancer cells. Anticancer Drugs 17:297–305PubMedCrossRefGoogle Scholar
  109. Tani N, Ohtsuru M, Hata T (1974a) Studies on bacterial myrosinase.1. Isolation of myrosinase producing microorganism. Agric Biol Chem 38:1617–1622Google Scholar
  110. Tani N, Ohtsuru M, Hata T (1974b) Studies on bacterial myrosinase.2. Purification and general characteristics of bacterial myrosinase produced by enterobacter-cloacae. Agric Biol Chem 38:1623–1630Google Scholar
  111. Thapliyal R, Maru GB (2001) Inhibition of cytochrome P450 isozymes by curcumins in vitro and in vivo. Food Chem Toxicol 39:541–547PubMedCrossRefGoogle Scholar
  112. Thejass P, Kuttan G (2007) Allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) inhibit tumour-specific angiogenesis by downregulating nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) production. Nitric Oxide 16:247–257PubMedCrossRefGoogle Scholar
  113. Thornalley PJ (2002) Isothiocyanates: mechanism of cancer chemopreventive action. Anticancer Drugs 13:331–338PubMedCrossRefGoogle Scholar
  114. Toroser D, Thormann CE, Osborn TC et al (1995) Rflp mapping of quantitative trait loci controlling seed aliphatic-glucosinolate content in oilseed rape (Brassica napus L.). Theor Appl Genet 91:802–808CrossRefGoogle Scholar
  115. Traka M, Gasper AV, Smith JA et al (2005) Transcriptome analysis of human colon Caco-2 cells exposed to sulforaphane. J Nutr 135:1865–1872PubMedGoogle Scholar
  116. Tseng E, Kamath A, Morris ME (2002) Effect of organic isothiocyanates on the P-glycoprotein- and MRP1-mediated transport of daunomycin and vinblastine. Pharm Res 19:1509–1515PubMedCrossRefGoogle Scholar
  117. Vallejo F, Tomas-Barberan FA, Garcia-Viguera C (2002) Glucosinolates and vitamin C content in edible parts of broccoli florets after domestic cooking. Eur Food Res Technol 215:310–316CrossRefGoogle Scholar
  118. Verhagen H, Poulsen HE, Loft S et al (1995) Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis 16:969–970PubMedCrossRefGoogle Scholar
  119. Verhoeven DT, Verhagen H, Goldbohm RA et al (1997) A review of mechanisms underlying anticarcinogenicity by brassica vegetables. Chem Biol Interact 103:79–129PubMedCrossRefGoogle Scholar
  120. Visanji JM, Duthie SJ, Pirie L et al (2004) Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase cell cycle arrest, DNA damage, and G2/M checkpoint activation. J Nutr 134:3121–3126PubMedGoogle Scholar
  121. Wang L, Liu D, Ahmed T et al (2004a) Targeting cell cycle machinery as a molecular mechanism of sulforaphane in prostate cancer prevention. Int J Oncol 24:187–192PubMedGoogle Scholar
  122. Wang LI, Giovannucci EL, Hunter D et al (2004b) Dietary intake of cruciferous vegetables, glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population. Cancer Causes Control 15:977–985PubMedCrossRefGoogle Scholar
  123. Wang LG, Beklemisheva A, Liu XM et al (2007) Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer. Mol Carcinog 46:24–31PubMedCrossRefGoogle Scholar
  124. Wentzell AM, Rowe HC, Hansen BG et al (2007) Linking metabolic QTLs with network and cis-eQTLs controlling biosynthetic pathways. PLoS Genet 3:1687–1701PubMedCrossRefGoogle Scholar
  125. Wierinckx A, Breve J, Mercier D et al (2005) Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J Neuroimmunol 166:132–143PubMedCrossRefGoogle Scholar
  126. Xiao D, Singh SV (2002) Phenethyl isothiocyanate-induced apoptosis in p53-deficient PC-3 human prostate cancer cell line is mediated by extracellular signal-regulated kinases. Cancer Res 62:3615–3619PubMedGoogle Scholar
  127. Xiao D, Singh SV (2007) Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res 67:2239–2246PubMedCrossRefGoogle Scholar
  128. Xiao D, Srivastava SK, Lew KL et al (2003) Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis. Carcinogenesis 24:891–897PubMedCrossRefGoogle Scholar
  129. Xiao D, Johnson CS, Trump DL et al (2004) Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells. Mol Cancer Ther 3:567–575PubMedGoogle Scholar
  130. Xiao D, Lew KL, Zeng Y et al (2006) Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential. Carcinogenesis 27:2223–2234PubMedCrossRefGoogle Scholar
  131. Xu C, Shen G, Chen C et al (2005) Suppression of NF-κB and NF-κB-regulated gene expression by sulforaphane and PEITC through IκBα, IKK pathway in human prostate cancer PC-3 cells. Oncogene 24:4486–4495PubMedCrossRefGoogle Scholar
  132. Yang YM, Conaway CC, Chiao JW et al (2002) Inhibition of benzo(a) pyrene-induced lung tumorigenesis in A/J mice by dietary N-acetylcysteine conjugates of benzyl and phenethyl isothiocyanates during the postinitiation phase is associated with activation of mitogen-activated protein kinases and p53 activity and induction of apoptosis. Cancer Res 62:2–7PubMedGoogle Scholar
  133. Ye L, Zhang Y (2001) Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of Phase 2 detoxification enzymes. Carcinogenesis 22:1987–1992PubMedCrossRefGoogle Scholar
  134. Zhang Y (2000) Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells. Carcinogenesis 21:1175–1182PubMedCrossRefGoogle Scholar
  135. Zhang Y, Callaway EC (2002) High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J 364:301–307PubMedGoogle Scholar
  136. Zhang DD, Hannink M (2003) 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 23:8137–8151PubMedCrossRefGoogle Scholar
  137. Zhang Y, Kensler TW, Cho CG et al (1994) Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci USA 91:3147–3150PubMedCrossRefGoogle Scholar
  138. Zhang Y, Kolm RH, Mannervik B et al (1995) Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. Biochem Biophys Res Commun 206:748–755PubMedCrossRefGoogle Scholar
  139. Zhang R, Loganathan S, Humphreys I et al (2006) Benzyl isothiocyanate-induced DNA damage causes G2/M cell cycle arrest and apoptosis in human pancreatic cancer cells. J Nutr 136:2728–2734PubMedGoogle Scholar
  140. Zhao B, Seow A, Lee EJ et al (2001) Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore. Cancer Epidemiol Biomarkers Prev 10:1063–1067PubMedGoogle Scholar
  141. Zhao H, Lin J, Grossman HB et al (2007) Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk. Int J Cancer 120:2208–2213PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Phytochemicals and Health ProgrammeInstitute of Food ResearchNorwichUK

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