Sulforaphane as a Promising Molecule for Fighting Cancer

Conference paper
Part of the Cancer Treatment and Research book series (CTAR, volume 159)


Cancer is a complex disease characterized by multiple genetic and molecular alterations involving transformation, deregulation of apoptosis, proliferation, invasion, angiogenesis, and metastasis. To grow, invade, and metastasize, tumors need host components and primary dysfunction in the tumor microenvironment, in addition to cell dysfunction, can be crucial for carcinogenesis. A great variety of phytochemicals have been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific. Because of the enormous biological diversity of cancer, this pleiotropism might constitute an advantage. Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive/chemotherapeutic agents. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables. SFN has proved to be an effective chemoprotective agent in cell culture, in carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. It promoted potent cytostatic and cytotoxic effects orchestrated by the modulation of different molecular targets. Cell vulnerability to SFN-mediated apoptosis was subject to regulation by cell-cycle-dependent mechanisms but was independent of a mutated p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its potential therapeutic benefit in clinical settings. Overall, SFN appears to be an effective and safe chemopreventive molecule and a promising tool to fight cancer.


Sulforaphane Isothiocyanates Phase I and II enzymes Angiogenesis Metastatic process 







Cytochrome P450






NAD(P)H:quinone oxidoreductase 1

Keap 1

Kelch-like ECH-associated protein 1




Heterocyclic amines




Cyclin-dependent kinase


Histone deacetylase


Vascular endothelial growth factor




Nuclear factor (erythroid-derived 2)-like 2

Hif-1 α

Hypoxia-inducible factor-1 α


Heme oxygenase-1


Antioxidant response element


  1. 1.
    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
  2. 2.
    Bacon JR, Williamson G, Garner RC et al (2003) Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes. Carcinogenesis 24:1903–1911PubMedCrossRefGoogle Scholar
  3. 3.
    Bacon JR, Plumb GW, Howie AF et al (2007) Dual action of sulforaphane in the regulation of thioredoxin reductase and thioredoxin in human HepG2 and Caco-2 cells. J Agric Food Chem 55:1170–1176PubMedCrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    Barcelo S, Mace K, Pfeifer AM et al (1998) Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5-f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane. Mutat Res 402:111–120PubMedCrossRefGoogle Scholar
  6. 6.
    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
  7. 7.
    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
  8. 8.
    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
  9. 9.
    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
  10. 10.
    Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257PubMedCrossRefGoogle Scholar
  11. 11.
    Chambers AF, Matrisian LM (1997) Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89:1260–1270PubMedCrossRefGoogle Scholar
  12. 12.
    Chaudhuri D, Orsulic S, Ashok BT (2007) Antiproliferative activity of sulforaphane in Akt-overexpressing ovarian cancer cells. Mol Cancer Ther 6:334–345PubMedCrossRefGoogle Scholar
  13. 13.
    Chen MJ, Tang WY, Hsu CW et al (2012) Apoptosis induction in primary human colorectal cancer cell lines and retarded tumor growth in SCID mice by sulforaphane. Evid Based Complement Alternat Med 2012:415231PubMedGoogle Scholar
  14. 14.
    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
  15. 15.
    Choi S, Lew KL, Xiao H et al (2007) D, L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1. Carcinogenesis 28:151–162PubMedCrossRefGoogle Scholar
  16. 16.
    Clarke JD, Hsu A, Yu Z et al (2011) Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res 55:999–1009PubMedCrossRefGoogle Scholar
  17. 17.
    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
  18. 18.
    Cornblatt BS, Ye L, Dinkova-Kostova AT et al (2007) Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis 28:1485–1490PubMedCrossRefGoogle Scholar
  19. 19.
    Dashwood RH (2002) Modulation of heterocyclic amine-induced mutagenicity and carcinogenicity: an ‘A-to-Z’ guide to chemopreventive agents, promoters, and transgenic models. Mutat Res 511:89–112PubMedCrossRefGoogle Scholar
  20. 20.
    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
  21. 21.
    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
  22. 22.
    Fidler IJ (1978) Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer Res 38:2651–2660PubMedGoogle Scholar
  23. 23.
    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
  24. 24.
    Fimognari C, Nusse M, Berti F et al (2003) Sulforaphane modulates cell cycle and apoptosis in transformed and non-transformed human T lymphocytes. Ann NY Acad Sci 1010:393–398PubMedCrossRefGoogle Scholar
  25. 25.
    Fimognari C, Nusse M, Berti F et al (2004) Isothiocyanates as novel cytotoxic and cytostatic agents: molecular pathway on human transformed and non-transformed cells. Biochem Pharmacol 68:1133–1138PubMedCrossRefGoogle Scholar
  26. 26.
    Fimognari C, Berti F, Cantelli-Forti G et al (2005) Effect of sulforaphane on micronucleus induction in cultured human lymphocytes by four different mutagens. Environ Mol Mutagen 46:260–267PubMedCrossRefGoogle Scholar
  27. 27.
    Fimognari C, Sangiorgi L, Capponcelli S et al (2005) A mutated p53 status did not prevent the induction of apoptosis by sulforaphane, a promising anti-cancer drug. Invest New Drugs 23:195–203PubMedCrossRefGoogle Scholar
  28. 28.
    Fimognari C, Nusse M, Lenzi M et al (2006) Sulforaphane increases the efficacy of doxorubicin in mouse fibroblasts characterized by p53 mutations. Mutat Res 601:92–101PubMedCrossRefGoogle Scholar
  29. 29.
    Fimognari C, Lenzi M, Sciuscio D et al (2007) Cell-cycle specificity of sulforaphane-mediated apoptosis in Jurkat T-leukemia cells. In Vivo 21:377–380PubMedGoogle Scholar
  30. 30.
    Fimognari C, Lenzi M, Sciuscio D et al (2007) Combination of doxorubicin and sulforaphane for reversing doxorubicin-resistant phenotype in mouse fibroblasts with p53Ser220 mutation. Ann NY Acad Sci 1095:62–69PubMedCrossRefGoogle Scholar
  31. 31.
    Fimognari C, Lenzi M, Cantelli-Forti G et al (2008) Induction of differentiation in human promyelocytic cells by the isothiocyanate sulforaphane. In Vivo 22:317–320PubMedGoogle Scholar
  32. 32.
    Gamet-Payrastre L, Lumeau S, Gasc N et al (1998) Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anticancer Drugs 9:141–148PubMedCrossRefGoogle Scholar
  33. 33.
    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
  34. 34.
    Gills JJ, Jeffery EH, Matusheski NV et al (2006) Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion. Cancer Lett 236:72–79PubMedCrossRefGoogle Scholar
  35. 35.
    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
  36. 36.
    Hamsa TP, Thejass P, Kuttan G (2011) Induction of apoptosis by sulforaphane in highly metastatic B16F–10 melanoma cells. Drug Chem Toxicol 34:332–340PubMedCrossRefGoogle Scholar
  37. 37.
    Hu C, Nikolic D, Eggler AL et al (2012) Screening for natural chemoprevention agents that modify human Keap1. Anal Biochem 421:108–114PubMedCrossRefGoogle Scholar
  38. 38.
    Itoh K, Wakabayashi N, Katoh Y et al (2003) Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 8:379–391PubMedCrossRefGoogle Scholar
  39. 39.
    Jackson SJ, Singletary KW (2004) Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis 25:219–227PubMedCrossRefGoogle Scholar
  40. 40.
    Jackson SJ, Singletary KW (2004) Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr 134:2229–2236PubMedGoogle Scholar
  41. 41.
    Jackson SJ, Singletary KW, Venema RC (2007) Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Vascul Pharmacol 46:77–84PubMedCrossRefGoogle Scholar
  42. 42.
    Jakubikova J, Sedlak J, Mithen R et al (2005) Role of PI3 K/Akt and MEK/ERK signaling pathways in sulforaphane- and erucin-induced phase II enzymes and MRP2 transcription, G2/M arrest and cell death in Caco-2 cells. Biochem Pharmacol 69:1543–1552PubMedCrossRefGoogle Scholar
  43. 43.
    Jakubikova J, Cervi D, Ooi M et al (2011) Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma. Haematologica 96:1170–1179PubMedCrossRefGoogle Scholar
  44. 44.
    Jee HG, Lee KE, Kim JB et al (2011) Sulforaphane inhibits oral carcinoma cell migration and invasion in vitro. Phytother Res 25:1623–1628PubMedCrossRefGoogle Scholar
  45. 45.
    Jeong WS, Kim IW, Hu R et al (2004) Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway. Pharm Res 21:661–670PubMedCrossRefGoogle Scholar
  46. 46.
    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
  47. 47.
    Jones SB, Brooks JD (2006) Modest induction of phase 2 enzyme activity in the F-344 rat prostate. BMC Cancer 6:62PubMedCrossRefGoogle Scholar
  48. 48.
    Kalpana Deepa Priya D, Gayathri R, Sakthisekaran D (2011) Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene. Biomed Pharmacother 65:9–16PubMedCrossRefGoogle Scholar
  49. 49.
    Kaminski BM, Steinhilber D, Stein JM et al (2012) Phytochemicals resveratrol and sulforaphane as potential agents for enhancing the anti-tumor activities of conventional cancer therapies. Curr Pharm Biotechnol 13:137–146PubMedCrossRefGoogle Scholar
  50. 50.
    Kanematsu S, Yoshizawa K, Uehara N et al (2011) Sulforaphane inhibits the growth of KPL-1 human breast cancer cells in vitro and suppresses the growth and metastasis of orthotopically transplanted KPL-1 cells in female athymic mice. Oncol Rep 26:603–608PubMedGoogle Scholar
  51. 51.
    Kang HJ, Hong YB, Kim HJ et al (2012) Bioactive food components prevent carcinogenic stress via Nrf2 activation in BRCA1 deficient breast epithelial cells. Toxicol Lett 209:154–160PubMedCrossRefGoogle Scholar
  52. 52.
    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
  53. 53.
    Kim MR, Zhou L, Park BH et al (2011) Induction of G/M arrest and apoptosis by sulforaphane in human osteosarcoma U2-OS cells. Mol Med Report 4:929–934Google Scholar
  54. 54.
    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 241:275–280PubMedCrossRefGoogle Scholar
  55. 55.
    Lee JM, Johnson JA (2004) An important role of Nrf2-ARE pathway in the cellular defense mechanism. J Biochem Mol Biol 37:139–143PubMedCrossRefGoogle Scholar
  56. 56.
    Liotta LA, Tryggvason K, Garbisa S et al (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284:67–68PubMedCrossRefGoogle Scholar
  57. 57.
    Liotta LA (1984) Tumor invasion and metastases: role of the basement membrane. Warner-Lambert Parke-Davis award lecture. Am J Pathol 117:339–348PubMedGoogle Scholar
  58. 58.
    Liotta LA (1986) Tumor invasion and metastases–role of the extracellular matrix: Rhoads memorial award lecture. Cancer Res 46:1–7PubMedCrossRefGoogle Scholar
  59. 59.
    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
  60. 60.
    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
  61. 61.
    Misiewicz I, Skupinska K, Kasprzycka-Guttman T (2003) Sulforaphane and 2-oxohexyl isothiocyanate induce cell growth arrest and apoptosis in L-1210 leukemia and ME-18 melanoma cells. Oncol Rep 10:2045–2050PubMedGoogle Scholar
  62. 62.
    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
  63. 63.
    Morimitsu Y, Nakagawa Y, Hayashi K et al (2002) A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway. J Biol Chem 277:3456–3463PubMedCrossRefGoogle Scholar
  64. 64.
    Munday R, Munday CM (2004) 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 52:1867–1871PubMedCrossRefGoogle Scholar
  65. 65.
    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
  66. 66.
    Myzak MC, Dashwood WM, Orner GA et al (2006) Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. FASEB J 20:506–508PubMedGoogle Scholar
  67. 67.
    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
  68. 68.
    Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284:13291–13295PubMedCrossRefGoogle Scholar
  69. 69.
    Nicolson GL (1982) Cancer metastasis. Organ colonization and the cell-surface properties of malignant cells. Biochim Biophys Acta 695:113–176PubMedGoogle Scholar
  70. 70.
    Pappa G, Lichtenberg M, Iori R et al (2006) Comparison of growth inhibition profiles and mechanisms of apoptosis induction in human colon cancer cell lines by isothiocyanates and indoles from Brassicaceae. Mutat Res 599:76–87PubMedCrossRefGoogle Scholar
  71. 71.
    Park SY, Kim GY, Bae SJ et al (2007) Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3. Oncol Rep 18:181–187PubMedGoogle Scholar
  72. 72.
    Parkin DM, Bray F, Ferlay J et al (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156PubMedCrossRefGoogle Scholar
  73. 73.
    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
  74. 74.
    Pham NA, Jacobberger JW, Schimmer AD et al (2004) The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Mol Cancer Ther 3:1239–1248PubMedGoogle Scholar
  75. 75.
    Pledgie-Tracy A, Sobolewski MD, Davidson NE (2007) Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol Cancer Ther 6:1013–1021PubMedCrossRefGoogle Scholar
  76. 76.
    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 25:1302–1309PubMedCrossRefGoogle Scholar
  77. 77.
    Shan Y, Sun C, Zhao X et al (2006) Effect of sulforaphane on cell growth, G(0)/G(1) phase cell progression and apoptosis in human bladder cancer T24 cells. Int J Oncol 29:883–888PubMedGoogle Scholar
  78. 78.
    Shapiro TA, Fahey JW, Dinkova-Kostova AT et al (2006) Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Nutr Cancer 55:53–62PubMedCrossRefGoogle Scholar
  79. 79.
    Shen G, Xu C, Chen C et al (2006) p53-independent G1 cell cycle arrest of human colon carcinoma cells HT-29 by sulforaphane is associated with induction of p21CIP1 and inhibition of expression of cyclin D1. Cancer Chemother Pharmacol 57:317–327PubMedCrossRefGoogle Scholar
  80. 80.
    Shishu, Kaur IP (2003) Inhibition of mutagenicity of food-derived heterocyclic amines by sulforaphane–a constituent of broccoli. Indian J Exp Biol 41:216–219PubMedGoogle Scholar
  81. 81.
    Singh AV, Xiao D, Lew KL et al (2004) 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
  82. 82.
    Singh SV, Herman-Antosiewicz A, Singh AV et al (2004) 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
  83. 83.
    Singh SV, Srivastava SK, Choi S et al (2005) Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem 280:19911–19924PubMedCrossRefGoogle Scholar
  84. 84.
    Singletary K, MacDonald C (2000) Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells by dibenzoylmethane and sulforaphane. Cancer Lett 155:47–54PubMedCrossRefGoogle Scholar
  85. 85.
    Stetler-Stevenson WG, Hewitt R, Corcoran M (1996) Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Semin Cancer Biol 7:147–154PubMedCrossRefGoogle Scholar
  86. 86.
    Suh N, Luyengi L, Fong HH et al (1995) Discovery of natural product chemopreventive agents utilizing HL-60 cell differentiation as a model. Anticancer Res 15:233–239PubMedGoogle Scholar
  87. 87.
    Surh YJ (2003) Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 3:768–780PubMedCrossRefGoogle Scholar
  88. 88.
    Svehlikova V, Wang S, Jakubikova J et al (2004) Interactions between sulforaphane and apigenin in the induction of UGT1A1 and GSTA1 in CaCo-2 cells. Carcinogenesis 25:1629–1637PubMedCrossRefGoogle Scholar
  89. 89.
    Tang L, Zhang Y (2004) Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. J Nutr 134:2004–2010PubMedGoogle Scholar
  90. 90.
    Thejass P, Kuttan G (2006) Antimetastatic activity of sulforaphane. Life Sci 78:3043–3050PubMedCrossRefGoogle Scholar
  91. 91.
    Wang L, Liu D, Ahmed T et al (2004) Targeting cell cycle machinery as a molecular mechanism of sulforaphane in prostate cancer prevention. Int J Oncol 24:187–192PubMedGoogle Scholar
  92. 92.
    Xu C, Shen G, Yuan X et al (2006) ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells. Carcinogenesis 27:437–445PubMedCrossRefGoogle Scholar
  93. 93.
    Zhang Y, Talalay P, Cho CG et al (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci USA 89:2399–2403PubMedCrossRefGoogle Scholar
  94. 94.
    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
  95. 95.
    Zhong H, Bowen JP (2006) Antiangiogenesis drug design: multiple pathways targeting tumor vasculature. Curr Med Chem 13:849–862PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Dipartimento di Scienze per la Qualità della VitaUniversity of BolognaRiminiItaly
  2. 2.Dipartimento di Farmacia e BiotecnologieUniversity of BolognaBolognaItaly

Personalised recommendations