Anti-angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health

Biochemical Pharmacology

Volumn 81, Issue 3, 2011, Pages 327-336

  Cavell, Breeze E ^a   Syed Alwi, Sharifah S ^a   Donlevy, Alison ^a   Packham, Graham ^a  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

Angiogenesis; Hypoxia inducible factor; Isothiocyanates; Nuclear factor B; Tubulin

Indexed keywords

ALLYLL ISOTHIOCYANATE; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; BENZYL ISOTHIOCYANATE; BEVACIZUMAB; GLUTATHIONE; HYPOXIA INDUCIBLE FACTOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; ISOTHIOCYANIC ACID DERIVATIVE; MYC PROTEIN; OXYGEN; PHENETHYL ISOTHIOCYANATE; PLACEBO; REACTIVE OXYGEN METABOLITE; SULFORAPHANE; TRANSCRIPTION FACTOR AP 1; TUBULIN; UNCLASSIFIED DRUG;

ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL STRAIN MCF 7; DRUG BIOAVAILABILITY; DRUG MECHANISM; FOOD DRUG INTERACTION; HELA CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LIVER CELL CARCINOMA; LUNG CANCER; MAXIMUM PLASMA CONCENTRATION; MELANOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN MODIFICATION; WATERCRESS;

EID: 78650691587     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2010.10.005     Document Type: Note

References (102)

1. K.L. Cheung, and A.N. Kong Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention AAPS J 12 2010 87 97
2. N. Juge, R.F. Mithen, and M. Traka Molecular basis for chemoprevention by sulforaphane: a comprehensive review Cell Mol Life Sci 64 2007 1105 1127
3. J.D. Hayes, M.O. Kelleher, and I.M. Eggleston The cancer chemopreventive actions of phytochemicals derived from glucosinolates Eur J Nutr 47 Suppl. 2 2008 73 88
4. J.D. Clarke, R.H. Dashwood, and E. Ho Multi-targeted prevention of cancer by sulforaphane Cancer Lett 269 2008 291 304
5. Y. Zhang Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action Mutat Res 555 2004 173 190
6. W.H. Mennicke, K. Gorler, G. Krumbiegel, D. Lorenz, and N. Rittmann Studies on the metabolism and excretion of benzyl isothiocyanate in man Xenobiotica 18 1988 441 447
7. S.M. Getahun, and F.L. Chung Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress Cancer Epidemiol Biomarkers Prev 8 1999 447 451
8. T.A. Shapiro, J.W. Fahey, K.L. Wade, K.K. Stephenson, and P. Talalay Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans Cancer Epidemiol Biomarkers Prev 10 2001 501 508
9. P. Brennan, C.C. Hsu, N. Moullan, N. Szeszenia-Dabrowska, J. Lissowska, and D. Zaridze Effect of cruciferous vegetables on lung cancer in patients stratified by genetic status: a Mendelian randomisation approach Lancet 366 2005 1558 1560
10. A.V. Gasper, A. Al-Janobi, J.A. Smith, J.R. Bacon, P. Fortun, and C. Atherton Glutathione S-transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli Am J Clin Nutr 82 2005 1283 1291
11. L.I. Wang, E.L. Giovannucci, D. Hunter, D. Neuberg, L. Su, and D.C. Christiani Dietary intake of cruciferous vegetables. Glutathione S-transferase (GST) polymorphisms and lung cancer risk in a Caucasian population Cancer Causes Control 15 2004 977 985
12. Y. Zhang, and E.C. Callaway High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate Biochem J 364 2002 301 307
13. Y. Zhang Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells Carcinogenesis 21 2000 1175 1182
14. D. Trachootham, Y. Zhou, H. Zhang, Y. Demizu, Z. Chen, and H. Pelicano Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate Cancer Cell 10 2006 241 252
15. R.H. Dashwood, and E. Ho Dietary agents as histone deacetylase inhibitors: sulforaphane and structurally related isothiocyanates Nutr Rev 66 Suppl. 1 2008 S36 S38
16. L. Mi, X. Wang, S. Govind, B.L. Hood, T.D. Veenstra, and T.P. Conrads The role of protein binding in induction of apoptosis by phenethyl isothiocyanate and sulforaphane in human non-small lung cancer cells Cancer Res 67 2007 6409 6416
17. K. Xu, and P.J. Thornalley Involvement of glutathione metabolism in the cytotoxicity of the phenethyl isothiocyanate and its cysteine conjugate to human leukaemia cells in vitro Biochem Pharmacol 61 2001 165 177
18. W. Li, and A.N. Kong Molecular mechanisms of Nrf2-mediated antioxidant response Mol Carcinog 48 2009 91 104
19. T.O. Khor, S. Yu, and A.N. Kong Dietary cancer chemopreventive agents - targeting inflammation and Nrf2 signaling pathway Planta Med 74 2008 1540 1547
20. R.A. Sharma, A.L. Harris, A.G. Dalgleish, W.P. Steward, and K.J. O'Byrne Angiogenesis as a biomarker and target in cancer chemoprevention Lancet Oncol 2 2001 726 732
21. V. Baeriswyl, and G. Christofori The angiogenic switch in carcinogenesis Semin Cancer Biol 19 2009 329 337
22. M. Asakage, N.H. Tsuno, J. Kitayama, T. Tsuchiya, S. Yoneyama, and J. Yamada Sulforaphane induces inhibition of human umbilical vein endothelial cells proliferation by apoptosis Angiogenesis 9 2006 83 91
23. E. Bertl, H. Bartsch, and C. Gerhauser Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention Mol Cancer Ther 5 2006 575 585
24. D. Xiao, and S.V. Singh Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo Cancer Res 67 2007 2239 2246
25. P. Thejass, and G. Kuttan Inhibition of endothelial cell differentiation and proinflammatory cytokine production during angiogenesis by allyl isothiocyanate and phenyl isothiocyanate Integr Cancer Ther 6 2007 389 399
26. S.J. Jackson, K.W. Singletary, and R.C. Venema Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization Vascul Pharmacol 46 2007 77 84
27. P. Thejass, and G. Kuttan 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 2007 247 257
28. G. Kallifatidis, V. Rausch, B. Baumann, A. Apel, B.M. Beckermann, and A. Groth Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling Gut 58 2009 949 963
29. K. Nakayama Cellular signal transduction of the hypoxia response J Biochem 146 2009 757 765
30. V.A. Carroll, and M. Ashcroft Targeting the molecular basis for tumour hypoxia Expert Rev Mol Med 7 2005 1 16
31. X.H. Wang, B.E. Cavell, S.S. Syed Alwi, and G. Packham Inhibition of hypoxia inducible factor by phenethyl isothiocyanate Biochem Pharmacol 78 2009 261 272
32. H. Yao, H. Wang, Z. Zhang, B.H. Jiang, J. Luo, and X. Shi Sulforaphane inhibited expression of hypoxia-inducible factor-1alpha in human tongue squamous cancer cells and prostate cancer cells Int J Cancer 123 2008 1255 1261
33. J. Hu, J. Straub, D. Xiao, S.V. Singh, H.S. Yang, and N. Sonenberg Phenethyl isothiocyanate, a cancer chemopreventive constituent of cruciferous vegetables, inhibits cap-dependent translation by regulating the level and phosphorylation of 4E-BP1 Cancer Res 67 2007 3569 3573
34. M. Kleijn, G.C. Scheper, H.O. Voorma, and A.A. Thomas Regulation of translation initiation factors by signal transduction Eur J Biochem 253 1998 531 544
35. A. De Benedetti, and A.L. Harris eIF4E expression in tumors: its possible role in progression of malignancies Int J Biochem Cell Biol 31 1999 59 72 (Pubitemid 29094790)
36. A. Toschi, E. Lee, N. Gadir, M. Ohh, and D.A. Foster Differential dependence of hypoxia-inducible factors 1 alpha and 2 alpha on mTORC1 and mTORC2 J Biol Chem 283 2008 34495 34499
37. Y. Mizukami, Y. Kohgo, and D.C. Chung Hypoxia inducible factor-1 independent pathways in tumor angiogenesis Clin Cancer Res 13 2007 5670 5674
38. Y. Mizukami, W.S. Jo, E.M. Duerr, M. Gala, J. Li, and X. Zhang Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells Nat Med 11 2005 992 997
39. E.T. Wong, and V. Tergaonkar Roles of NF-kappaB in health and disease: mechanisms and therapeutic potential Clin Sci (Lond) 116 2009 451 465
40. E.P. Cummins, E. Berra, K.M. Comerford, A. Ginouves, K.T. Fitzgerald, and F. Seeballuck Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity Proc Natl Acad Sci USA 103 2006 18154 18159
41. E. Heiss, C. Herhaus, K. Klimo, H. Bartsch, and C. Gerhauser Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms J Biol Chem 276 2001 32008 32015
42. W.S. Jeong, I.W. Kim, R. Hu, and A.N. Kong Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway Pharm Res 21 2004 661 670
43. S.K. Srivastava, and S.V. Singh 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 2004 1701 1709
44. C. Xu, G. Shen, C. Chen, C. Gelinas, and A.N. Kong 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 2005 4486 4495
45. Y. Shan, K. Wu, W. Wang, S. Wang, N. Lin, and R. Zhao Sulforaphane down-regulates COX-2 expression by activating p38 and inhibiting NF-kappaB-DNA-binding activity in human bladder T24 cells Int J Oncol 34 2009 1129 1134
46. D.O. Moon, M.O. Kim, S.H. Kang, Y.H. Choi, and G.Y. Kim Sulforaphane suppresses TNF-alpha-mediated activation of NF-kappaB and induces apoptosis through activation of reactive oxygen species-dependent caspase-3 Cancer Lett 274 2009 132 142
47. H.K. Na, and Y.J. Surh Transcriptional regulation via cysteine thiol modification: a novel molecular strategy for chemoprevention and cytoprotection Mol Carcinog 45 2006 368 380
48. J.W. Fahey, X. Haristoy, P.M. Dolan, T.W. Kensler, I. Scholtus, and K.K. Stephenson 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 2002 7610 7615
49. M. Ramos-Gomez, M.K. Kwak, P.M. Dolan, K. Itoh, M. Yamamoto, and P. Talalay Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice Proc Natl Acad Sci USA 98 2001 3410 3415
50. Y.F. Xia, B.Q. Ye, Y.D. Li, J.G. Wang, X.J. He, and X. Lin Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50 J Immunol 173 2004 4207 4217
51. P. Anand, A.B. Kunnumakkara, K.B. Harikumar, K.S. Ahn, V. Badmaev, and B.B. Aggarwal Modification of cysteine residue in p65 subunit of nuclear factor-kappaB (NF-kappaB) by picroliv suppresses NF-kappaB-regulated gene products and potentiates apoptosis Cancer Res 68 2008 8861 8870
52. M.S. Byun, J. Choi, and D.M. Jue Cysteine-179 of IkappaB kinase beta plays a critical role in enzyme activation by promoting phosphorylation of activation loop serines Exp Mol Med 38 2006 546 552
53. C. Jobin, C.A. Bradham, M.P. Russo, B. Juma, A.S. Narula, and D.A. Brenner Curcumin blocks cytokine-mediated NF-kappa B activation and proinflammatory gene expression by inhibiting inhibitory factor I-kappa B kinase activity J Immunol 163 1999 3474 3483
54. M.K. Pandey, S.K. Sandur, B. Sung, G. Sethi, A.B. Kunnumakkara, and B.B. Aggarwal Butein, a tetrahydroxychalcone, inhibits nuclear factor (NF)-kappaB and NF-kappaB-regulated gene expression through direct inhibition of IkappaBalpha kinase beta on cysteine 179 residue J Biol Chem 282 2007 17340 17350
55. D.F. Lee, H.P. Kuo, M. Liu, C.K. Chou, W. Xia, and Y. Du KEAP1 E3 ligase-mediated downregulation of NF-kappaB signaling by targeting IKKbeta Mol Cell 36 2009 131 140
56. J. Hess, P. Angel, and M. Schorpp-Kistner AP-1 subunits: quarrel and harmony among siblings J Cell Sci 117 2004 5965 5973
57. W. Jochum, E. Passegue, and E.F. Wagner AP-1 in mouse development and tumorigenesis Oncogene 20 2001 2401 2412
58. D. Schmidt, B. Textor, O.T. Pein, A.H. Licht, S. Andrecht, and M. Sator-Schmitt Critical role for NF-kappaB-induced JunB in VEGF regulation and tumor angiogenesis EMBO J 26 2007 710 719
59. W.S. Jeong, I.W. Kim, R. Hu, and A.N. Kong Modulation of AP-1 by natural chemopreventive compounds in human colon HT-29 cancer cell line Pharm Res 21 2004 649 660
60. M. Zhu, Y. Zhang, S. Cooper, E. Sikorski, J. Rohwer, and G.T. Bowden Phase II enzyme inducer, sulforaphane, inhibits UVB-induced AP-1 activation in human keratinocytes by a novel mechanism Mol Carcinog 41 2004 179 186
61. S.E. Dickinson, T.F. Melton, E.R. Olson, J. Zhang, K. Saboda, and G.T. Bowden 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 2009 7103 7110
62. J. Li, S. Yao, and Y. Zhang The role of c-Jun in the AP-1 activation induced by naturally occurring isothiocyanates Food Chem Toxicol 43 2005 1373 1380
63. C. Xu, G. Shen, X. Yuan, J.H. Kim, A. Gopalkrishnan, and Y.S. Keum 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 2006 437 445
64. S.J. Jackson, and K.W. Singletary Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization J Nutr 134 2004 2229 2236
65. T.K. Smith, E.K. Lund, M.L. Parker, R.G. Clarke, and I.T. Johnson Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells Carcinogenesis 25 2004 1409 1415
66. L. Mi, Z. Xiao, B.L. Hood, S. Dakshanamurthy, X. Wang, and S. Govind Covalent binding to tubulin by isothiocyanates. A mechanism of cell growth arrest and apoptosis J Biol Chem 283 2008 22136 22146
67. L. Mi, N. Gan, A. Cheema, S. Dakshanamurthy, X. Wang, and D.C. Yang Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes J Biol Chem 284 2009 17039 17051
68. P. Yin, T. Kawamura, M. He, D.K. Vanaja, and C.Y. Young Phenethyl isothiocyanate induces cell cycle arrest and reduction of alpha- and beta-tubulin isotypes in human prostate cancer cells Cell Biol Int 33 2009 57 64
69. D. Escuin, E.R. Kline, and P. Giannakakou Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1alpha accumulation and activity by disrupting microtubule function Cancer Res 65 2005 9021 9028
70. M.C. Myzak, E. Ho, and R.H. Dashwood Dietary agents as histone deacetylase inhibitors Mol Carcinog 45 2006 443 446
71. L. Ellis, H. Hammers, and R. Pili Targeting tumor angiogenesis with histone deacetylase inhibitors Cancer Lett 280 2009 145 153
72. Y. Ji, and M.E. Morris Determination of phenethyl isothiocyanate in human plasma and urine by ammonia derivatization and liquid chromatography-tandem mass spectrometry Anal Biochem 323 2003 39 47
73. S.S. Syed Alwi, B.E. Cavell, U. Telang, M.E. Morris, B.M. Parry, and G. Packham In vivo modulation of 4E binding protein 1 (4E-BP1) phosphorylation by watercress: a pilot study Br J Nutr 2010 1 9
74. A.A. Al Janobi, R.F. Mithen, A.V. Gasper, P.N. Shaw, R.J. Middleton, and C.A. Ortori Quantitative measurement of sulforaphane, iberin and their mercapturic acid pathway metabolites in human plasma and urine using liquid chromatography-tandem electrospray ionisation mass spectrometry J Chromatogr B Analyt Technol Biomed Life Sci 844 2006 223 234
75. C.I. Gill, S. Haldar, L.A. Boyd, R. Bennett, J. Whiteford, and M. Butler Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults Am J Clin Nutr 85 2007 504 510
76. M.C. Myzak, P. Tong, W.M. Dashwood, R.H. Dashwood, and E. Ho Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects Exp Biol Med (Maywood) 232 2007 227 234
77. D. Trachootham, H. Zhang, W. Zhang, L. Feng, M. Du, and Y. Zhou Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism Blood 112 2008 1912 1922
78. C. Fimognari, M. Lenzi, and P. Hrelia Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications Curr Drug Metab 9 2008 668 678
79. L. Chen, S.N. Mohr, and C.S. Yang Decrease of plasma and urinary oxidative metabolites of acetaminophen after consumption of watercress by human volunteers Clin Pharmacol Ther 60 1996 651 660
80. R.L. Moreno, U.M. Kent, K. Hodge, and P.F. Hollenberg Inactivation of cytochrome P450 2E1 by benzyl isothiocyanate Chem Res Toxicol 12 1999 582 587
81. C.C. Conaway, D. Jiao, and F.L. Chung Inhibition of rat liver cytochrome P450 isozymes by isothiocyanates and their conjugates: a structure-activity relationship study Carcinogenesis 17 1996 2423 2427
82. T.J. Smith, Z. Guo, F.P. Guengerich, and C.S. Yang Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P450 1A2 and its inhibition by phenethyl isothiocyanate Carcinogenesis 17 1996 809 813
83. H. Ishizaki, J.F. Brady, S.M. Ning, and C.S. Yang Effect of phenethyl isothiocyanate on microsomal N-nitrosodimethylamine metabolism and other monooxygenase activities Xenobiotica 20 1990 255 264
84. K. Maheo, F. Morel, S. Langouet, H. Kramer, E. Le Ferrec, and B. Ketterer Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes Cancer Res 57 1997 3649 3652
85. C. Xu, X. Yuan, Z. Pan, G. Shen, J.H. Kim, and S. Yu Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2 Mol Cancer Ther 5 2006 1918 1926
86. W.S. Jeong, Y.S. Keum, C. Chen, M.R. Jain, G. Shen, and J.H. Kim Differential expression and stability of endogenous nuclear factor E2-related factor 2 (Nrf2) by natural chemopreventive compounds in HepG2 human hepatoma cells J Biochem Mol Biol 38 2005 167 176
87. Y.S. Keum, E.D. Owuor, B.R. Kim, R. Hu, and A.N. Kong Involvement of Nrf2 and JNK1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent phenethyl isothiocyanate (PEITC) Pharm Res 20 2003 1351 1356
88. Y. Zhang, L. Tang, and V. Gonzalez Selected isothiocyanates rapidly induce growth inhibition of cancer cells Mol Cancer Ther 2 2003 1045 1052
89. N. Miyoshi, K. Uchida, T. Osawa, and Y. Nakamura A link between benzyl isothiocyanate-induced cell cycle arrest and apoptosis: involvement of mitogen-activated protein kinases in the Bcl-2 phosphorylation Cancer Res 64 2004 2134 2142
90. N.A. Pham, J.W. Jacobberger, A.D. Schimmer, P. Cao, M. Gronda, and D.W. Hedley 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 2004 1239 1248
91. L. Gamet-Payrastre, P. Li, S. Lumeau, G. Cassar, M.A. Dupont, and S. Chevolleau Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells Cancer Res 60 2000 1426 1433
92. D. Xiao, C.S. Johnson, D.L. Trump, and S.V. Singh 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 2004 567 575
93. K. Xu, and P.J. Thornalley Studies on the mechanism of the inhibition of human leukaemia cell growth by dietary isothiocyanates and their cysteine adducts in vitro Biochem Pharmacol 60 2000 221 231
94. R. Yu, S. Mandlekar, K.J. Harvey, D.S. Ucker, and A.N. Kong Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity Cancer Res 58 1998 402 408
95. D. Xiao, Y. Zeng, S. Choi, K.L. Lew, J.B. Nelson, and S.V. Singh Caspase-dependent apoptosis induction by phenethyl isothiocyanate, a cruciferous vegetable-derived cancer chemopreventive agent, is mediated by Bak and Bax Clin Cancer Res 11 2005 2670 2679 (Pubitemid 40569468)
96. Y.F. Kuang, and Y.H. Chen Induction of apoptosis in a non-small cell human lung cancer cell line by isothiocyanates is associated with P53 and P21 Food Chem Toxicol 42 2004 1711 1718
97. Y. Nakamura, M. Kawakami, A. Yoshihiro, N. Miyoshi, H. Ohigashi, and K. Kawai Involvement of the mitochondrial death pathway in chemopreventive benzyl isothiocyanate-induced apoptosis J Biol Chem 277 2002 8492 8499
98. E.S. Hwang, and H.J. Lee 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 2006 421 430
99. E.S. Hwang, and H.J. Lee Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells J Nutr Biochem 17 2006 837 846
100. P. Thejass, and G. Kuttan Antimetastatic activity of sulforaphane Life Sci 78 2006 3043 3050
101. E. Heiss, and C. Gerhauser Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA Antioxid Redox Signal 7 2005 1601 1611
102. L. Mi, X. Wang, S. Govind, B.L. Hood, T.D. Veenstra, and T.P. Conrads The role of protein binding in induction of apoptosis by phenethyl isothiocyanate and sulforaphane in human non-small lung cancer cells Cancer Res. 67 2007 6409 6416