The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates

Carcinogenesis

Volumn 33, Issue 1, 2012, Pages 2-9

  Zhang, Yuesheng ^a  

^a ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TUBULIN; BENZYL ISOTHIOCYANATE; BETA TUBULIN; CYTOCHROME P450 2A1; CYTOCHROME P450 2B1; GELATINASE A; GELATINASE B; GLUTATHIONE; HISTONE DEACETYLASE; ISOTHIOCYANIC ACID; KELCH LIKE ECH ASSOCIATED PROTEIN 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 1; PHENETHYL ISOTHIOCYANATE; PROTEIN BCL 2; PROTEIN BCL XL; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR NRF2; VASCULOTROPIN; VASCULOTROPIN RECEPTOR;

ANGIOGENESIS; BIOAVAILABILITY; BIOLOGICAL ACTIVITY; CANCER CELL; CANCER CELL CULTURE; CANCER GROWTH; CANCER INVASION; CELL CYCLE ARREST; CELL DEATH; CELL PROLIFERATION; CELL SURVIVAL; CELL TRANSPORT; CHEMICAL REACTION; CHEMOPROPHYLAXIS; DIETARY INTAKE; DOWN REGULATION; DRUG BINDING; DRUG CONJUGATION; DRUG METABOLISM; DRUG UPTAKE; HUMAN; LUNG CARCINOGENESIS; METASTASIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; REVIEW; SINGLE DRUG DOSE; UBIQUITINATION; UPREGULATION;

EID: 84855369813     PISSN: 01433334     EISSN: 14602180     Source Type: Journal    
DOI: 10.1093/carcin/bgr255     Document Type: Review

References (130)

1. Zhang,Y. et al. (1994) Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Res., 54, 1976s-1981s.
2. Hecht,S.S. (1995) Chemoprevention by isothiocyanates. J. Cell. Biochem. Suppl., 22, 195-209.
3. Hecht,S.S. (2000) Inhibition of carcinogenesis by isothiocyanates. Drug Metab. Rev., 32, 395-411.
4. Conaway,C.C. et al. (2002) Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr. Drug Metab., 3, 233-255.
5. Zhang,Y. (2004) Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action. Mutat. Res., 555, 173-190.
6. Zhang,Y. et al. (2006) Vegetable-derived isothiocyanates: anti-proliferative activity and mechanism of action. Proc. Nutr. Soc., 65, 68-75.
7. Nakamura,Y. et al. (2006) Cell death induction by isothiocyanates and their underlying molecular mechanisms. Biofactors, 26, 123-134.
8. Cheung,K.L. et al. (2010) Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J., 12, 87-97.
9. Zhang,Y. (2010) Allyl isothiocyanate as a cancer chemopreventive phytochemical. Mol. Nutr. Food Res., 54, 127-135.
10. Zhang,Y. et al. (2007) Discovery and development of sulforaphane as a cancer chemopreventive phytochemical. Acta Pharmacol. Sin., 28, 1343-1354.
11. Mi,L. et al. (2011) Proteins as binding targets of isothiocyanates in cancer prevention. Carcinogenesis, 32, 1405-1413.
12. Bhattacharya,A. et al. (2010) Inhibition of bladder cancer development by allyl isothiocyanate. Carcinogenesis, 31, 281-286.
13. Srivastava,S.K. et al. (2003) Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. Carcinogenesis, 24, 1665-1670.
14. Musk,S.R. et al. (1993) Allyl isothiocyanate is selectively toxic to transformed cells of the human colorectal tumour line HT29. Carcinogenesis, 14, 2079-2083.
15. Gamet-Payrastre,L. et al. (2000) Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res., 60, 1426-1433.
16. Gamet-Payrastre,L. et al. (1998) Selective cytostatic and cytotoxic effects of glucosinolates hydrolysis products on human colon cancer cells in vitro. Anticancer Drugs, 9, 141-148.
17. Xiao,D. 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, 891-897.
18. Uematsu,Y. et al. (2002) Determination of isothiocyanates and related compounds in mustard extract and horseradish extract used as natural food additives. Shokuhin Eiseigaku Zasshi, 43, 10-17.
19. Gil,V. et al. (1983) Benzylglucosinolate degradation in Lepidium sativum: effects of plant age and time of autolysis. Phytochemistry, 19, 1365-1368.
20. Chung,F.L. et al. (1992) Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal. Cancer Epidemiol. Biomarkers Prev., 1, 383-388.
21. Zhang,Y. et al. (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl Acad. Sci. USA, 89, 2399-2403.
22. Fahey,J.W. et al. (1997) Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl Acad. Sci. USA, 94, 10367-10372.
23. Fahey,J.W. et al. (2001) The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry, 56, 5-51.
24. Brusewitz,G. et al. (1977) The metabolism of benzyl isothiocyanate and its cysteine conjugate. Biochem. J., 162, 99-107.
25. Mennicke,W.H. et al. (1988) Studies on the metabolism and excretion of benzyl isothiocyanate in man. Xenobiotica, 18, 441-447.
26. Kassahun,K. et al. (1997) Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates. Chem. Res. Toxicol., 10, 1228-1233.
27. Gasper,A.V. et al. (2005) Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am. J. Clin. Nutr., 82, 1283-1291.
28. Egner,P.A. et al. (2008) Quantification of sulforaphane mercapturic acid pathway conjugates in human urine by high-performance liquid chromatography and isotope-dilution tandem mass spectrometry. Chem. Res. Toxicol., 21, 1991-1996.
29. Ioannou,Y.M. et al. (1984) Allyl isothiocyanate: comparative disposition in rats and mice. Toxicol. Appl. Pharmacol., 75, 173-181.
30. Bollard,M. et al. (1997) The disposition of allyl isothiocyanate in the rat and mouse. Food Chem. Toxicol., 35, 933-943.
31. Jiao,D. et al. (1994) Identification and quantification of the N-acetylcysteine conjugate of allyl isothiocyanate in human urine after ingestion of mustard. Cancer Epidemiol. Biomarkers Prev., 3, 487-492.
32. Zhang,Y. (2011) The 1,2-benzenedithiole-based cyclocondensation assay, a valuable tool for measurement of chemopreventive isothiocyanates. Crit. Rev. Food Sci. Nutr. in press, doi: 10.1080/10408398.2010.503288.
33. Kolm,R.H. et al. (1995) Isothiocyanates as substrates for human glutathione transferases: structure-activity studies. Biochem. J., 311, 453-459.
34. Ye,L. et al. (2002) Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans. Clin. Chim. Acta, 316, 43-53.
35. Conaway,C.C. et al. (2001) Decomposition rates of isothiocyanate conjugates determine their activity as inhibitors of cytochrome p.450 enzymes. Chem. Res. Toxicol., 14, 1170-1176.
36. Shapiro,T.A. et al. (1998) Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol. Biomarkers Prev., 7, 1091-1100.
37. Eklind,K.I. et al. (1990) Distribution and metabolism of the natural anticarcinogen phenethyl isothiocyanate in A/J mice. Carcinogenesis, 11, 2033-2036.
38. Gorler,K. et al. (1982) The metabolism of benzyl isothiocyanate and its cysteine conjugate in guinea-pigs and rabbits. Xenobiotica, 12, 535-542.
39. Bruggeman,I.M. et al. (1986) Glutathione- and cysteine-mediated cytotoxicity of allyl and benzyl isothiocyanate. Toxicol. Appl. Pharmacol., 83, 349-359.
40. Baillie,T.A. et al. (1991) Glutathione: a vehicle for the transport of chemically reactive metabolites in vivo. Acc. Chem. Res., 24, 264-270.
41. Tang,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, 297-305.
42. Chiao,J.W. et al. (2002) Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int. J. Oncol., 20, 631-636.
43. Conaway,C.C. 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, 8548-8557.
44. Zhang,Y. et al. (1998) Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic phase 2 enzymes. Cancer Res., 58, 4632-4639.
45. Zhang,Y. (2000) Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells. Carcinogenesis, 21, 1175-1182.
46. Zhang,Y. (2001) Molecular mechanism of rapid cellular accumulation of anticarcinogenic isothiocyanates. Carcinogenesis, 22, 425-431.
47. Zhang,Y. et al. (2002) High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem. J., 364, 301-307.
48. Anderson,M.E. (1998) Glutathione: an overview of biosynthesis and modulation. Chem. Biol. Interact., 111-112, 1-14.
49. Mi,L. et al. (2007) The role of protein binding in induction of apoptosis by phenethyl isothiocyanate and sulforaphane in human non-small lung cancer cells. Cancer Res., 67, 6409-6416.
50. Mi,L. et al. (2010) A cautionary note on using N-acetylcysteine as an antagonist to assess isothiocyanate-induced reactive oxygen species-mediated apoptosis. Anal. Biochem., 405, 269-271.
51. Callaway,E.C. et al. (2004) Cellular accumulation of dietary anticarcinogenic isothiocyanates is followed by transporter-mediated export as dithiocarbamates. Cancer Lett., 204, 23-31.
52. Tseng,E. et al. (2002) Effect of organic isothiocyanates on the Pglycoprotein-and MRP1-mediated transport of daunomycin and vinblastine. Pharm. Res., 19, 1509-1515.
53. Ji,Y. et al. (2004) Effect of organic isothiocyanates on breast cancer resistance protein (ABCG2)-mediated transport. Pharm. Res., 21, 2261-2269.
54. Ji,Y. et al. (2005) Membrane transport of dietary phenethyl isothiocyanate by ABCG2 (breast cancer resistance protein). Mol. Pharm., 2, 414-419.
55. Hollenberg,P.F. et al. (2008) Mechanism-based inactivation of human cytochromes p450s: experimental characterization, reactive intermediates, and clinical implications. Chem. Res. Toxicol., 21, 189-205.
56. Smith,T.J. et al. (1993) Mechanisms of inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone bioactivation in mouse by dietary phenethyl isothiocyanate. Cancer Res., 53, 3276-3282.
57. Morse,M.A. et al. (1989) Effects of aromatic isothiocyanates on tumorigenicity, O6-methylguanine formation, and metabolism of the tobaccospecific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung. Cancer Res., 49, 2894-2897.
58. Jiao,D. et al. (1996) The essential role of the functional group in alkyl isothiocyanates for inhibition of tobacco nitrosamine-induced lung tumorigenesis. Carcinogenesis, 17, 755-759.
59. Conaway,C.C. et al. (1996) Inhibition of rat liver cytochrome P450 isozymes by isothiocyanates and their conjugates: a structure-activity relationship study. Carcinogenesis, 17, 2423-2427.
60. Goosen,T.C. et al. (2000) Inactivation of cytochrome P450 2B1 by benzyl isothiocyanate, a chemopreventative agent from cruciferous vegetables. Chem. Res. Toxicol., 13, 1349-1359.
61. Fahey,J.W. 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, 7610-7615.
62. Iida,K. et al. (2004) Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res., 64, 6424-6431.
63. Sussan,T.E. et al. (2009) Targeting Nrf2 with the triterpenoid CDDOimidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc. Natl Acad. Sci. USA, 106, 250-255.
64. Ding,Y. et al. (2010) Sulforaphane inhibits 4-aminobiphenyl-induced DNA damage in bladder cells and tissues. Carcinogenesis, 31, 1999-2003.
65. Stewart,D. et al. (2003) Degradation of transcription factor Nrf2 via the ubiquitin-proteasome pathway and stabilization by cadmium. J. Biol. Chem., 278, 2396-2402.
66. Kobayashi,A. et al. (2004) Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol., 24, 7130-7139.
67. Zhang,D.D. (2006) Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab. Rev., 38, 769-789.
68. Dinkova-Kostova,A.T. et al. (2005) The role of Keap1 in cellular protective responses. Chem. Res. Toxicol., 18, 1779-1791.
69. Prawan,A. et al. (2008) Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression. Pharm. Res., 25, 836-844.
70. Ernst,I.M. et al. (2011) Allyl-, butyl- and phenylethyl-isothiocyanate activate Nrf2 in cultured fibroblasts. Pharmacol. Res., 63, 233-240.
71. Dinkova-Kostova,A.T. 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, 11908-11913.
72. Hong,F. et al. (2005) Identification of sensor cysteines in human Keap1 modified by the cancer chemopreventive agent sulforaphane. Chem. Res. Toxicol., 18, 1917-1926.
73. Zhang,D.D. et al. (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, 8137-8151.
74. Thimmulappa,R.K. et al. (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res., 62, 5196-5203.
75. Xu,C. et al. (2006) 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, 8293-8296.
76. Geng,F. et al. (2011) Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via BCL-2 phosphorylation. J. Biol. Chem, 286, 32259-32267.
77. Xu,W. et al. (2009) Natural product derivative Bis(4-fluorobenzyl)trisulfide inhibits tumor growth by modification of beta-tubulin at Cys 12 and suppression of microtubule dynamics. Mol. Cancer Ther., 8, 3318-3330.
78. Zhang,X. et al. (2007) Identification of arsenic-binding proteins in human breast cancer cells. Cancer Lett., 255, 95-106.
79. Shan,B. et al. (1999) Selective, covalent modification of beta-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors. Proc. Natl Acad. Sci. USA, 96, 5686-5691.
80. Bai,R. et al. (1996) Identification of cysteine 354 of beta-tubulin as part of the binding site for the A ring of colchicine. J. Biol. Chem., 271, 12639-12645.
81. Bai,R. et al. (2000) Mapping the binding site of colchicinoids on betatubulin. 2-chloroacetyl-2-demethylthiocolchicine covalently reacts predominantly with cysteine 239 and secondarily with cysteine 354. J. Biol. Chem., 275, 40443-40452.
82. Mi,L. et al. (2009) Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes. J. Biol. Chem., 284, 17039-17051.
83. Mi,L. et al. (2008) Covalent binding to tubulin by isothiocyanates. A mechanismof cell growth arrest and apoptosis. J. Biol. Chem., 283, 22136-22146.
84. Jackson,S.J. et al. (2004) Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J. Nutr., 134, 2229-2236.
85. Barthelman,M. et al. (1998) Inhibitory effects of perillyl alcohol on UVBinduced murine skin cancer and AP-1 transactivation. Cancer Res., 58, 711-716.
86. Huang,C. et al. (1997) Inhibition of ultraviolet B-induced activator protein-1 (AP-1) activity by aspirin in AP-1-luciferase transgenic mice. J. Biol. Chem., 272, 26325-26331.
87. Zhu,M. et al. (2004) Phase II enzyme inducer, sulforaphane, inhibits UVB-induced AP-1 activation in human keratinocytes by a novel mechanism. Mol. Carcinog., 41, 179-186.
88. Dickinson,S.E. et al. (2009) Inhibition of activator protein-1 by sulforaphane involves interaction with cysteine in the cFos DNA-binding domain: implications for chemoprevention of UVB-induced skin cancer. Cancer Res., 69, 7103-7110.
89. Jeong,W.S. et al. (2004) Modulation of AP-1 by natural chemopreventive compounds in human colon HT-29 cancer cell line. Pharm. Res., 21, 649-660.
90. Patten,E.J. et al. (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, 149-155.
91. Li,J. et al. (2005) The role of c-Jun in the AP-1 activation induced by naturally occurring isothiocyanates. Food Chem. Toxicol., 43, 1373-1380.
92. Cross,J.V. et al. (2007) The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase. BMC Cancer, 7, 183.
93. Hu,R. et al. (2003) The roles of JNK and apoptotic signaling pathways in PEITC-mediated responses in human HT-29 colon adenocarcinoma cells. Carcinogenesis, 24, 1361-1367.
94. Chen,Y.R. et al. (2002) Phenylethyl isothiocyanate induces apoptotic signaling via suppressing phosphatase activity against c-Jun N-terminal kinase. J. Biol. Chem., 277, 39334-39342.
95. Youn,H.S. et al. (2010) Sulforaphane suppresses oligomerization of TLR4 in a thiol-dependent manner. J. Immunol., 184, 411-419.
96. Jeong,W.S. et al. (2004) Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway. Pharm. Res., 21, 661-670.
97. Srivastava,S.K. et al. (2004) Cell cycle arrest, apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzyl isothiocyanate against human pancreatic cancer cells. Carcinogenesis, 25, 1701-1709.
98. Xu,C. et al. (2005) Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells. Oncogene, 24, 4486-4495.
99. Batra,S. et al. (2010) Benzyl isothiocyanate-mediated inhibition of histone deacetylase leads to NF-kappaB turnoff in human pancreatic carcinoma cells. Mol. Cancer. Ther., 9, 1596-1608.
100. Myzak,M.C. et al. (2006) Dietary agents as histone deacetylase inhibitors. Mol. Carcinog., 45, 443-446.
101. Wang,L.G. et al. (2007) Dual action on promoter demethylation and chromatin by an isothiocyanate restored GSTP1 silenced in prostate cancer. Mol. Carcinog., 46, 24-31.
102. Wang,L.G. et al. (2008) De-repression of the p21 promoter in prostate cancer cells by an isothiocyanate via inhibition of HDACs and c-Myc. Int. J. Oncol., 33, 375-380.
103. Dashwood,R.H. et al. (2007) Dietary histone deacetylase inhibitors: from cells to mice to man. Semin. Cancer Biol., 17, 363-369.
104. Singh,S.V. 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, 25813-25822.
105. Xiao,D. 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, 567-575.
106. Mi,L. et al. (2011) Isothiocyanates inhibit proteasome activity and proliferation of multiple myeloma cells. Carcinogenesis, 32, 216-223.
107. Xiao,D. et al. (2006) Benzyl isothiocyanate-induced apoptosis in human breast cancer cells is initiated by reactive oxygen species and regulated by Bax and Bak. Mol. Cancer Ther., 5, 2931-2945.
108. Wu,S.J. et al. (2005) Effects of antioxidants and caspase-3 inhibitor on the phenylethyl isothiocyanate-induced apoptotic signaling pathways in human PLC/PRF/5 cells. Eur. J. Pharmacol., 518, 96-106.
109. Park,S.Y. 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, 181-187.
110. Shankar,S. et al. (2008) Sulforaphane enhances the therapeutic potential of TRAIL in prostate cancer orthotopic model through regulation of apoptosis, metastasis, and angiogenesis. Clin. Cancer Res., 14, 6855-6866.
111. Tang,L. et al. (2005) Mitochondria are the primary target in isothiocyanate-induced apoptosis in human bladder cancer cells. Mol. Cancer Ther., 4, 1250-1259.
112. Warin,R. et al. (2010) Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Mol. Carcinog., 49, 500-507.
113. Xiao,D. et al. (2007) Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res., 67, 2239-2246.
114. Bertl,E. et al. (2006) Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol. Cancer Ther., 5, 575-585.
115. Kumar,A. et al. (2009) Antiangiogenic and proapoptotic activities of allyl isothiocyanate inhibit ascites tumor growth in vivo. Integr. Cancer Ther., 8, 75-87.
116. Yao,H. et al. (2008) Sulforaphane inhibited expression of hypoxia-inducible factor-1alpha in human tongue squamous cancer cells and prostate cancer cells. Int. J. Cancer., 123, 125512-125561.
117. Wang,X.H. et al. (2009) Inhibition of hypoxia inducible factor by phenethyl isothiocyanate. Biochem. Pharmacol., 78, 261-272.
118. Hwang,E.S. et al. (2006) Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in SK-Hep 1 human hepatoma cells. Exp. Biol. Med. (Maywood), 231, 421-430.
119. Hwang,E.S. et al. (2006) Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells. J. Nutr. Biochem., 17, 837-846.
120. Hwang,E.S. et al. (2008) Benzyl isothiocyanate inhibits metalloproteinase-2/-9 expression by suppressing the mitogen-activated protein kinase in SK-Hep1 human hepatoma cells. Food Chem. Toxicol., 46, 2358-2364.
121. Sahu,R.P. et al. (2009) The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. J. Natl. Cancer Inst., 101, 176-193.
122. Gong,A. et al. (2009) Phenethyl isothiocyanate inhibits STAT3 activation in prostate cancer cells. Mol. Nutr. Food Res., 53, 878-886.
123. Hahm,E.R. et al. (2010) Sulforaphane inhibits constitutive and interleukin-6-induced activation of signal transducer and activator of transcription 3 in prostate cancer cells. Cancer Prev. Res. (Phila), 3, 484-494.
124. Zhang,Y. et al. (2005) Cancer-preventive isothiocyanates: dichotomous modulators of oxidative stress. Free Radic. Biol. Med., 38, 70-77.
125. Meng,T.-C. et al. (2006) Cys-oxidation of protein tyrosine phosphatases: its role in regulation of signal transduction and its involvement in human cancers. J. Cancer Mol., 2, 9-16.
126. Edman,P. (1956) On the mechanism of the phenyl isothiocyanate degradation of peptides. Acta Chem. Scand., 10, 761-765.
127. Nakamura,T. et al. (2009) Covalent modification of lysine residues by allyl isothiocyanate in physiological conditions: plausible transformation of isothiocyanate from thiol to amine. Chem. Res. Toxicol., 22, 536-542.
128. Brown,K.K. et al. (2009) Direct modification of the proinflammatory cytokine macrophage migration inhibitory factor by dietary isothiocyanates. J. Biol. Chem., 284, 32425-32433.
129. Swope,M. et al. (1998) Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. EMBO J., 17, 3534-3541.
130. Podhradsky,D. et al. (1979) Reactions of cysteine, its derivatives, glutathione coenzyme A, and dihydrolipoic acid with isothiocyanates. Experientia, 35, 154-155.