Cruciferous Vegetables, Isothiocyanates, and Prevention of Bladder Cancer

Current Pharmacology Reports

Volumn 1, Issue 4, 2015, Pages 272-282

  Veeranki, Omkara L ^a   Bhattacharya, Arup ^a   Tang, Li ^a   Marshall, James R ^a   Zhang, Yuesheng ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

Bladder cancer; Chemoprevention; Cruciferous vegetable; Isothiocyanate

Indexed keywords

CELECOXIB; CYCLIN B1; ISOTHIOCYANIC ACID; MULTIDRUG RESISTANCE ASSOCIATED PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 1; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROTEIN BCL 2; PROTEIN BCL XL; SURVIVIN; TOLL LIKE RECEPTOR 4;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BLADDER CANCER; BLADDER CANCER CELL LINE; CANCER INHIBITION; CANCER PREVENTION; CANCER RECURRENCE; CHEMOPROPHYLAXIS; G1 PHASE CELL CYCLE CHECKPOINT; G2 PHASE CELL CYCLE CHECKPOINT; GENE EXPRESSION REGULATION; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; TOXICITY; URETHRAL CATHETERIZATION; URINARY EXCRETION; VEGETABLE;

EID: 84960095662     PISSN: None     EISSN: 2198641X     Source Type: Journal    
DOI: 10.1007/s40495-015-0024-z     Document Type: Review

References (112)

1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.
2. Freedman ND, Silverman DT, Hollenbeck AR, et al. Association between smoking and risk of bladder cancer among men and women. JAMA. 2011;306(7):737–45.
3. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013;63(2):234–41.
4. Juffs HG, Moore MJ, Tannock IF. The role of systemic chemotherapy in the management of muscle-invasive bladder cancer. Lancet Oncol. 2002;3(12):738–47.
5. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol. 2013;64(4):639–53.
6. Metts MC, Metts JC, Milito SJ, et al. Bladder cancer: a review of diagnosis and management. J Natl Med Assoc. 2000;92(6):285–94.
7. Heney N, Proppe K, Prout Jr G, et al. Invasive bladder cancer: tumor configuration, lymphatic invasion and survival. J Urol. 1983;130(5):895–7.
8. Sylvester R, van der Meijden A, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466–77.
9. Kondas J, Kiss L, Hatar A, et al. The effect of intravesical mitomycin C on the recurrence of superficial (Ta-T1) bladder cancer. A Hungarian Multicenter Study. Int Urol Nephrol. 1999;31(4):451–6.
10. Knowles MA. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis. 2006;27(3):361–73.
11. Wu XR. Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer. 2005;5(9):713–25.
12. Botteman MF, Pashos CL, Redaelli A, et al. The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoeconomics. 2003;21(18):1315–30.
13. Jacobs BL, Lee CT, Montie JE. Bladder cancer in 2010: how far have we come? CA Cancer J Clin. 2010;60(4):244–72.
14. O'Donnell MA, Boehle A. Treatment options for BCG failures. World J Urol. 2006;24(5):481–7.
15. Hilton WM, Ercole B, Parekh DJ, et al. Efficacy of combined intravesical immunotherapy and chemotherapy for non-muscle invasive bladder cancer. Expert Rev Anticancer Ther. 2011;11(6):949–57.
16. Zhang Y. Allyl isothiocyanate as a cancer chemopreventive phytochemical. Mol Nutr Food Res. 2010;54(1):127–35.
17. Nakamura Y, Kawakami M, Yoshihiro A, et al. Involvement of the mitochondrial death pathway in chemopreventive benzyl isothiocyanate-induced apoptosis. J Biol Chem. 2002;277(10):8492–9.
18. Melchini A, Costa C, Traka M, et al. Erucin, a new promising cancer chemopreventive agent from rocket salads, shows anti-proliferative activity on human lung carcinoma A549 cells. Food Chem Toxicol. 2009;47(7):1430–6.
19. Aras U, Gandhi YA, Masso-Welch PA, et al. Chemopreventive and anti-angiogenic effects of dietary phenethyl isothiocyanate in an N-methyl nitrosourea-induced breast cancer animal model. Biopharm Drug Dispos. 2013;34(2):98–106.
20. Cheung KL, Kong AN. Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J. 2010;12(1):87–97.
21. Zhang Y, Tang L. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical. Acta Pharmacol Sin. 2007;28(9):1343–54.
22. Juge N, Mithen RF, Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci. 2007;64(9):1105–27.
23. Higdon JV, Delage B, Williams DE, et al. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007;55(3):224–36.
24. Kim SH, Sehrawat A, Singh SV. Dietary chemopreventative benzyl isothiocyanate inhibits breast cancer stem cells in vitro and in vivo. Cancer Prev Res. 2013;6(8):782–90.
25. Wang D, Upadhyaya B, Liu Y, et al. Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits proliferation in human cancer stem-like cells. BMC Cancer. 2014;14(1):591–603.
26. Li Y, Zhang T. Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts. Future Oncol. 2013;9(8):1097–103.
27. Li SH, Fu J, Watkins DN, et al. Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of Sonic hedgehog-GLI pathway. Mol Cell Biochem. 2013;373(1–2):217–27.
28. Hecht SS. Chemoprevention by isothiocyanates. J Cell Biochem Suppl. 1995;22(1):195–209.
29. Dinkova-Kostova AT. Chemoprotection against cancer by isothiocyanates: a focus on the animal models and the protective mechanisms. Top Curr Chem. 2013;329(1):179–201.
30. Hecht SS. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev. 2000;32(3–4):395–411.
31. Abbaoui B, Riedl KM, Ralston RA, et al. Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion. Mol Nutr Food Res. 2012;56(11):1675–87.
32. Bhattacharya A, Tang L, Li Y, et al. Inhibition of bladder cancer development by allyl isothiocyanate. Carcinogenesis. 2010;31(2):281–6.
33. Sehrawat A, Singh SV. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells. Cancer Prev Res. 2011;4(7):1107–17.
34. Warin R, Xiao D, Arlotti JA, et al. Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Mol Carcinog. 2010;49(5):500–7.
35. Matsui TA, Murata H, Sakabe T, et al. Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo. Oncol Rep. 2007;18(5):1263–8.
36. Boreddy SR, Pramanik KC, Srivastava SK. Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway. Clin Cancer Res. 2011;17(7):1784–95.
37. Singh AV, Xiao D, Lew KL, et al. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis. 2004;25(1):83–90.
38. Singh SV, Warin R, Xiao D, et al. Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells. Cancer Res. 2009;69(5):2117–25.
39. Khor TO, Cheung WK, Prawan A, et al. Chemoprevention of familial adenomatous polyposis in Apc(Min/+) mice by phenethyl isothiocyanate (PEITC). Mol Carcinog. 2008;47(5):321–5.
40. Myzak MC, Dashwood WM, Orner GA, et al. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc-minus mice. FASEB J. 2006;20(3):506–8.
41. Zhang Y. The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates. Carcinogenesis. 2012;33(1):2–9.
42. Zhang Y. Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells. Carcinogenesis. 2000;21(6):1175–82.
43. Jiao D, Eklind KI, Choi CI, et al. Structure-activity relationships of isothiocyanates as mechanism-based inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in A/J mice. Cancer Res. 1994;54(16):4327–33.
44. Bones AM, Rossiter JT. The myrosinase-glucosinolate system, its organisation and biochemistry. Physiol Plant. 1996;97(1):194–208.
45. Bernardi R, Negri A, Ronchi S, et al. Isolation of the epithiospecifier protein from oil-rape (Brassica napus ssp. oleifera) seed and its characterization. FEBS Lett. 2000;467(2–3):296–8.
46. Fenwick GR, Heaney RK. Glucosinolates and their breakdown products in cruciferous crops, foods, and feeding-stuffs. Food Chem. 1983;11(4):249–71.
47. Matusheski NV, Juvik JA, Jeffery EH. Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli. Phytochemistry. 2004;65(9):1273–81.
48. Rouzaud G, Young SA, Duncan AJ. Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Cancer Epidemiol Biomarkers Prev. 2004;13(1):125–31.
49. Zhang Y. Cancer-preventive isothiocyanates: Measurement of human exposure and mechanism of action. Mutat Res. 2004;555(1–2):173–90.
50. McNaughton SA, Marks GC. Development of a food composition database for the estimation of dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables. Br J Nutr. 2003;90(3):687–97.
51. Tang L, Paonessa JD, Zhang Y, et al. Total isothiocyanate yield from raw cruciferous vegetables commonly consumed in the United States. J Funct Foods. 2013;5(4):1996–2001.
52. Kolm RH, Danielson UH, Zhang Y, et al. Isothiocyanates as substrates for human glutathione transferases: structure-activity studies. Biochem J. 1995;311(2):453–9.
53. Chung FL, Morse MA, Eklind KI, et al. Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal. Cancer Epidemiol Biomarkers Prev. 1992;1(5):383–8.
54. Brusewitz G, Cameron BD, Chasseaud LF, et al. The metabolism of benzyl isothiocyanate and its cysteine conjugate. Biochem J. 1977;162(1):99–107.
55. Mennicke WH, Gorler K, Krumbiegel G, et al. Studies on the metabolism and excretion of benzyl isothiocyanate in man. Xenobiotica. 1988;18(4):441–7.
56. Kassahun K, Davis M, Hu P, et al. Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase i metabolites and glutathione conjugates. Chem Res Toxicol. 1997;10(11):1228–33.
57. Gasper AV, Al-Janobi A, Smith JA, et al. Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr. 2005;82(6):1283–91.
58. Egner PA, Kensler TW, Chen JG, et al. Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry. Chem Res Toxicol. 2008;21(10):1991–6.
59. Ioannou YM, Burka LT, Matthews HB. Allyl isothiocyanate: comparative disposition in rats and mice. Toxicol Appl Pharmacol. 1984;75(2):173–81.
60. Bollard M, Stribbling S, Mitchell S, et al. The disposition of allyl isothiocyanate in the rat and mouse. Food Chem Toxicol. 1997;35(10–11):933–43.
61. Jiao D, Ho CT, Foiles P, et al. Identification and quantification of the N-acetylcysteine conjugate of allyl isothiocyanate in human urine after ingestion of mustard. Cancer Epidemiol Biomarkers Prev. 1994;3(6):487–92.
62. Zhang Y. The 1,2-benzenedithiole-based cyclocondensation assay: a valuable tool for the measurement of chemopreventive isothiocyanates. Crit Rev Food Sci Nutr. 2012;52(6):525–32.
63. Ye L, Dinkova-Kostova AT, Wade KL, et al. Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans. Clin Chim Acta. 2002;316(1–2):43–53.
64. Egner PA, Chen JG, Wang JB, et al. Bioavailability of sulforaphane from two broccoli sprout beverages: results of a short-term, cross-over clinical trial in Qidong, China. Cancer Prev Res. 2011;4(3):384–95.
65. Veeranki OL, Bhattacharya A, Marshall JR, et al. Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention. Br J Nutr. 2012;2(109):25–32. This study shows that SF is rapidly eliminated through urinary excretion and that SF reaches different organs in vastly different concentrations. Hence, it provides a basis for prioritising organs for further chemopreventive study of SF and suggests that SF is highly promising cancer chemopreventive agent in the bladder.
66. Zhang Y, Munday R, Jobson HE, et al. Induction of GST and NQO1 in cultured bladder cells and in the urinary bladders of rats by an extract of broccoli (Brassica oleracea italica) sprouts. J Agric Food Chem. 2006;54(25):9370–6.
67. Munday R, Mhawech-Fauceglia P, Munday CM, et al. Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Cancer Res. 2008;68(5):1593–600.
68. Shapiro TA, Fahey JW, Wade KL, et al. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev. 1998;7(12):1091–100.
69. Tang L, Li G, Song L, et al. 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. 2006;17(3):297–305.
70. Conaway CC, Krzeminski J, Amin S, et al. Decomposition rates of isothiocyanate conjugates determine their activity as inhibitors of cytochrome p450 enzymes. Chem Res Toxicol. 2001;14(9):1170–6.
71. Anderson ME. Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact. 1998;111(1):1–14.
72. Zhang Y. Molecular mechanism of rapid cellular accumulation of anticarcinogenic isothiocyanates. Carcinogenesis. 2001;22(3):425–31.
73. Podhradsky D, Drobnica L, Kristian P. Reactions of cysteine, its derivatives, glutathione coenzyme A, and dihydrolipoic acid with isothiocyanates. Experientia. 1979;35(2):154–5.
74. Zhang Y, Li J, Tang L. Cancer-preventive isothiocyanates: dichotomous modulators of oxidative stress. Free Radic Biol Med. 2005;38(1):70–7.
75. Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J. 2002;364(Pt 1):301–7.
76. Callaway EC, Zhang Y, Chew W, et al. Cellular accumulation of dietary anticarcinogenic isothiocyanates is followed by transporter-mediated export as dithiocarbamates. Cancer Lett. 2004;204(1):23–31.
77. Ji Y, Morris ME. Membrane transport of dietary phenethyl isothiocyanate by ABCG2 (breast cancer resistance protein). Mol Pharm. 2005;2(5):414–9.
78. Tseng E, Kamath A, Morris ME. Effect of organic isothiocyanates on the P-glycoprotein- and MRP1-mediated transport of daunomycin and vinblastine. Pharm Res. 2002;19(10):1509–15.
79. Singh SV, Singh K. Cancer chemoprevention with dietary isothiocyanates mature for clinical translational research. Carcinogenesis. 2012;33(10):1833–42.
80. Zhang Y, Tang L, Gonzalez V. Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol Cancer Ther. 2003;2(10):1045–52.
81. Geng F, Tang L, Li Y, et al. Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J Biol Chem. 2011;286(37):32259–67. This article provides a novel anticancer mechanism by which AITC binds to cysteine residues of α- and β-tubulins, promoting its ubiquitination and degradation, and causing mitotic catastrophe through mitochondrion-mediated apoptosis. Bcl-2 phosphorylation by JNK activation is the molecular link between mitotic arrest and apoptosis in AITC treated UM-UC-3 BC cells.
82. Tang L, Zhang Y. Dietary isothiocyanates inhibit the growth of human bladder carcinoma cells. J Nutr. 2004;134(8):2004–10.
83. Tang L, Zhang Y. Mitochondria are the primary target in isothiocyanate-induced apoptosis in human bladder cancer cells. Mol Cancer Ther. 2005;4(8):1250–9.
84. Bhattacharya A, Li Y, Wade KL, et al. Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion. Carcinogenesis. 2010;31(12):2105–10.
85. Bhattacharya A, Li Y, Shi Y, et al. Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination. Carcinogenesis. 2013;34(11):2593–9. This study indicates that AITC together with pharmacologic inhibition of Cox-2 leads to enhanced anticancer efficacy and suggests that SF, which down regulates Cox-2, may complement AITC for inhibition of BC.
86. Wang F, Shan Y. Sulforaphane retards the growth of UM-UC-3 xenographs, induces apoptosis, and reduces survivin in athymic mice. Nutr Res. 2012;32(5):374–80.
87. Lee YM, Cho HJ, Ponnuraj SP, et al. Phenethyl isothiocyanate inhibits 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory responses in mouse skin. J Med Food. 2011;14(4):377–85.
88. Shan Y, Wu K, Wang W, et al. Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-kappaB-DNA-binding activity in human bladder T24 cells. Int J Oncol. 2009;34(4):1129–34.
89. Youn HS, Kim YS, Park ZY, et al. Sulforaphane suppresses oligomerization of TLR4 in a thiol-dependent manner. J Immunol. 2010;184(1):411–9.
90. Okazaki K, Yamagishi M, Son HY, et al. Simultaneous treatment with benzyl isothiocyanate, a strong bladder promoter, inhibits rat urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine. Nutr Cancer. 2002;42(2):211–6.
91. Bhattacharya A, Li Y, Geng F, Munday R, Zhang Y. The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(n-allylthiocarbamoyl)cysteine, inhibits the growth and muscle invasion of bladder cancer. Carcinogenesis. 2012;33(2):394–8. This study shows that the chemopreventive activity of the principal urinary metabolite of AITC, NAC-AITC, is similar to that of AITC in a preclinical orthotopical BC model; this provides further evidence of the chemopreventive activity of AITC in the bladder, as NAC-AITC is known to serve as a carrier of AITC.
92. Nishikawa A, Furukawa F, Uneyama C, et al. Chemopreventive effects of phenethyl isothiocyanate on lung and pancreatic tumorigenesis in N-nitrosobis(2-oxopropyl)amine-treated hamsters. Carcinogenesis. 1996;17(6):1381–4.
93. Kanematsu S, Yoshizawa K, Uehara N, et al. 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. 2011;26(3):603–8.
94. Tang L, Zhang Y, Jobson HE, Li J, et al. Potent activation of mitochondria-mediated apoptosis and arrest in s and m phases of cancer cells by a broccoli sprout extract. Mol Cancer Ther. 2006;5(4):935–44.
95. Shan Y, Sun C, Zhao X, et al. Effect of sulforaphane on cell growth, G(0)/G(1) phase cell progression and apoptosis in human bladder cancer T24 cells. Int J Oncol. 2006;29(4):883–8.
96. Park HS, Han MH, Kim GY, et al. Sulforaphane induces reactive oxygen species-mediated mitotic arrest and subsequent apoptosis in human bladder cancer 5637 cells. Food Chem Toxicol. 2014;64(1):157–65.
97. Mi L, Gan N, Cheema A, et al. Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes. J Biol Chem. 2009;284(25):17039–51.
98. Mi L, Xiao Z, Hood BL, et al. Covalent binding to tubulin by isothiocyanates. A mechanism of cell growth arrest and apoptosis. J Biol Chem. 2008;283(32):22136–46.
99. Jackson SJ, Singletary KW. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr. 2004;134(9):2229–36.
100. Miyoshi N, Uchida K, Osawa T, et al. A link between benzyl isothiocyanate-induced cell cycle arrest and apoptosis: involvement of mitogen-activated protein kinases in the Bcl-2 phosphorylation. Cancer Res. 2004;64(6):2134–42.
101. Jo GH, Kim GY, Kim WJ, et al. Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway. Int J Oncol. 2014;45(4):1497–506.
102. Kim SI, Kwon SM, Kim YS, et al. Association of cyclooxygenase-2 expression with prognosis of stage T1 grade 3 bladder cancer. Urology. 2002;60(5):816–21.
103. Shan Y, Wang X, Wang W, et al. p38 MAPK plays a distinct role in sulforaphane-induced up-regulation of ARE-dependent enzymes and down-regulation of COX-2 in human bladder cancer cells. Oncol Rep. 2010;23(4):1133–8.
104. Tang L, Zirpoli GR, Guru K, et al. Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17(4):938–44.
105. Michaud DS, Spiegelman D, Clinton SK, et al. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst. 1999;91(7):605–13.
106. Liu B, Mao Q, Lin Y, Zhou F, Xie L. The association of cruciferous vegetables intake and risk of bladder cancer: a meta-analysis. World J Urol. 2013;31(1):127–33. This meta-analysis of five cohorts and five case-control studies evaluated the relationship between cruciferous vegetables intake and risk of BC. It shows that high consumption of cruciferous vegetables is related to decreased risk of BC.
107. Tang L, Zirpoli GR, Guru K, et al. Intake of cruciferous vegetables modifies bladder cancer survival. Cancer Epidemiol Biomarkers Prev. 2010;19(7):1806–11.
108. Akagi K, Sano M, Ogawa K, et al. Involvement of toxicity as an early event in urinary bladder carcinogenesis induced by phenethyl isothiocyanate, benzyl isothiocyanate, and analogues in F344 rats. Toxicol Pathol. 2003;31(4):388–96.
109. Hasumura M, Imai T, Cho Y-M, et al. Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats. J Toxicol Sci. 2011;36(6):763–74.
110. Dunnick JK, Prejean JD, Haseman J, et al. Carcinogenesis bioassay of allyl isothiocyanate. Fundam Appl Toxicol. 1982;2(3):114–20.
111. Ogawa K, Hirose M, Sugiura S, et al. Dose-dependent promotion by phenylethyl isothiocyanate, a known chemopreventer, of two-stage rat urinary bladder and liver carcinogenesis. Nutr Cancer. 2001;40(2):134–9.
112. NAS/NRC: Poundage update of food chemicals. NAS/NRC 1982.