Cancer chemoprevention with dietary isothiocyanates mature for clinical translational research

Carcinogenesis

Volumn 33, Issue 10, 2012, Pages 1833-1842

  Singh, Shivendra V ^a,b   Singh, Kamayani ^b  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZYL ISOTHIOCYANATE; CARCINOGEN; CD31 ANTIGEN; CLUSTERIN; DEXTRO LEVO SULFORAPHANE; HYPOXIA INDUCIBLE FACTOR; ISOTHIOCYANIC ACID DERIVATIVE; NOTCH RECEPTOR; PHENETHYL ISOTHIOCYANATE; PROTEIN BCL 2; SULFORAPHANE; TRANSCRIPTION FACTOR REL; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; AUTOPHAGY; BLADDER CANCER; BLADDER CARCINOGENESIS; BREAST CARCINOGENESIS; BROCCOLI; CANCER CELL; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CANCER PREVENTION; CANCER RISK; CARCINOGEN DNA INTERACTION; CARCINOGENESIS; CELL DEATH; CELL JUNCTION; CELL PROLIFERATION; CELL RENEWAL; CHEMICAL STRUCTURE; DIET SUPPLEMENTATION; DIETARY INTAKE; DNA REPAIR; DRUG EFFICACY; DRUG SAFETY; ENZYME ACTIVATION; EPITHELIAL MESENCHYMAL TRANSITION; ESOPHAGUS CANCER; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; LIVER CARCINOGENESIS; LUNG CARCINOGENESIS; LUNG METASTASIS; M PHASE CELL CYCLE CHECKPOINT; MOLECULARLY TARGETED THERAPY; MOUTH SQUAMOUS CELL CARCINOMA; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; SKIN CANCER; SKIN CARCINOGENESIS; STOMACH CANCER; TRANSLATIONAL RESEARCH; VEGETABLE; WATERCRESS;

ANIMALS; AUTOPHAGY; BIOLOGICAL MARKERS; CHEMOPREVENTION; DIET; HUMANS; ISOTHIOCYANATES; MICE; MICE, TRANSGENIC; NEOPLASMS; NEOPLASMS, EXPERIMENTAL; RATS; RNA, MESSENGER; TRANSLATIONAL MEDICAL RESEARCH; URINARY BLADDER NEOPLASMS; VEGETABLES;

EID: 84866122895     PISSN: 01433334     EISSN: 14602180     Source Type: Journal    
DOI: 10.1093/carcin/bgs216     Document Type: Article

References (149)

1. Fisher, B. et al. (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl. Cancer Inst., 90, 1371-1388.
2. Cauley, J.A. et al. (2001) Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res. Treat., 65, 125-134.
3. Goss, P.E. et al. (2011) Exemestane for breast-cancer prevention in postmenopausal women. N. Engl. J. Med., 364, 2381-2391.
4. Powolny, A.A. et al. (2012) Slow but steady progress in cancer chemoprevention with phenethyl isothiocyanate: fulfilled promises and translational challenges. In: Sarkar, F.H. (ed.) Neutraceuticals and Cancer. Springer Science+Business Media B.V., The Netherlands, pp. 231-258.
5. Sehrawat, A. et al. (2012) Molecular mechanisms of cancer chemoprevention with benzyl isothiocyanate. In: Kong, A.N. (ed.) Inflammation and Cancer: Mechanisms and Dietary Approaches for Cancer Prevention. Taylor and Francis, New York, in press.
6. Clarke, J.D. et al. (2008) Multi-targeted prevention of cancer by sulforaphane. Cancer Lett., 269, 291-304.
7. Halkier, B.A. et al. (2006) Biology and biochemistry of glucosinolates. Annu. Rev. Plant Biol., 57, 303-333.
8. Fahey, J.W. et al. (2001) The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry, 56, 5-51.
9. Fahey, J.W. et al. (2012) Protection of humans by plant glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora. Cancer Prev. Res., 5, 603-611.
10. Hecht, S.S. (2000) Inhibition of carcinogenesis by isothiocyanates. Drug Metab. Rev., 32, 395-411.
11. Wattenberg, L.W. (1977) Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds. J. Natl. Cancer Inst., 58, 395-398.
12. Stoner, G.D. et al. (1991) Inhibitory effects of phenethyl isothiocyanate on N-nitrosobenzylmethylamine carcinogenesis in the rat esophagus. Cancer Res., 51, 2063-2068.
13. Chung, F.L. et al. (1996) Chemopreventive efficacy of arylalkyl isothiocyanates and N-acetylcysteine for lung tumorigenesis in Fischer rats. Cancer Res., 56, 772-778.
14. Zhang, Y. et al. (1994) Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc. Natl. Acad. Sci. U.S.A., 91, 3147-3150.
15. Morse, M.A. et al. (1989) Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate. Cancer Res., 49, 549-553.
16. Cheung, K.L. et al. (2010) Differential in vivo mechanism of chemoprevention of tumor formation in azoxymethane/dextran sodium sulfate mice by PEITC and DBM. Carcinogenesis, 31, 880-885.
17. Plate, A.Y. et al. (2006) Effects of indole-3-carbinol and phenethyl isothiocyanate on colon carcinogenesis induced by azoxymethane in rats. Carcinogenesis, 27, 287-292.
18. Yang, Y.M. et al. (2002) Inhibition of benzo(a)pyrene-induced lung tumorigenesis in A/J mice by dietary N-acetylcysteine conjugates of benzyl and phenethyl isothiocyanates during the postinitiation phase is associated with activation of mitogen-activated protein kinases and p53 activity and induction of apoptosis. Cancer Res., 62, 2-7.
19. Solt, D.B. et al. (2003) Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study of oral cancer chemoprevention. Cancer Lett., 202, 147-152.
20. Wattenberg, L.W. (1981) Inhibition of carcinogen-induced neoplasia by sodium cyanate, tert-butyl isocyanate, and benzyl isothiocyanate administered subsequent to carcinogen exposure. Cancer Res., 41, 2991-2994.
21. Lin, J.M. et al. (1993) Effects of isothiocyanates on tumorigenesis by benzo[a]pyrene in murine tumor models. Cancer Lett., 74, 151-159.
22. Hecht, S.S. et al. (2000) Effects of phenethyl isothiocyanate and benzyl isothiocyanate, individually and in combination, on lung tumorigenesis induced in A/J mice by benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Lett., 150, 49-56.
23. Wattenberg, L.W. (1987) Inhibitory effects of benzyl isothiocyanate administered shortly before diethylnitrosamine or benzo[a]pyrene on pulmonary and forestomach neoplasia in A/J mice. Carcinogenesis, 8, 1971-1973.
24. Sugie, S. et al. (1994) Inhibitory effects of benzyl thiocyanate and benzyl isothiocyanate on methylazoxymethanol acetate-induced intestinal carcinogenesis in rats. Carcinogenesis, 15, 1555-1560.
25. Hecht, S.S. et al. (2002) Benzyl isothiocyanate: an effective inhibitor of polycyclic aromatic hydrocarbon tumorigenesis in A/J mouse lung. Cancer Lett., 187, 87-94.
26. Sugie, S. et al. (1993) Inhibitory effects of benzyl isothiocyanate and benzyl thiocyanate on diethylnitrosamine-induced hepatocarcinogenesis in rats. Jpn. J. Cancer Res., 84, 865-870.
27. Kuroiwa, Y. et al. (2006) Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer Lett., 241, 275-280.
28. Chung, F.L. et al. (2000) Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis, 21, 2287-2291.
29. 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. U.S.A., 99, 7610-7615.
30. 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.
31. Gills, J.J. et al. (2006) Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion. Cancer Lett., 236, 72-79.
32. Ogawa, K. et al. (1998) Stage and organ dependent effects of 1-O-hexyl-2,3, 5-trimethylhydroquinone, ascorbic acid derivatives, n-heptadecane-8-10-dione and phenylethyl isothiocyanate in a rat multiorgan carcinogenesis model. Int. J. Cancer, 76, 851-856.
33. Ogawa, K. et al. (2001) Dose-dependent promotion by phenylethyl isothiocyanate, a known chemopreventer, of two-stage rat urinary bladder and liver carcinogenesis. Nutr. Cancer, 40, 134-139.
34. Sugiura, S. et al. (2003) Reversibility of proliferative lesions and induction of non-papillary tumors in rat urinary bladder treated with phenylethyl isothiocyanate. Carcinogenesis, 24, 547-553.
35. Takagi, H. et al. (2005) Limited tumor-initiating activity of phenylethyl isothiocyanate by promotion with sodium L-ascorbate in a rat two-stage urinary bladder carcinogenesis model. Cancer Lett., 219, 147-153.
36. Hirose, M. et al. (1998) Strong promoting activity of phenylethyl isothiocyanate and benzyl isothiocyanate on urinary bladder carcinogenesis in F344 male rats. Int. J. Cancer, 77, 773-777.
37. Okazaki, K. et al. (2002) Simultaneous treatment with benzyl isothiocyanate, a strong bladder promoter, inhibits rat urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine. Nutr. Cancer, 42, 211-216.
38. Okazaki, K. et al. (2003) Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl)nitrosamine in rats after initiation. Cancer Sci., 94, 948-952.
39. Michaud, D.S. et al. (1999) Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J. Natl. Cancer Inst., 91, 605-613.
40. Tang, L. et al. (2008) Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk. Cancer Epidemiol. Biomarkers Prev., 17, 938-944.
41. Tang, L. et al. (2010) Intake of cruciferous vegetables modifies bladder cancer survival. Cancer Epidemiol. Biomarkers Prev., 19, 1806-1811.
42. Musk, S.R. et al. (1993) The clastogenic effects of isothiocyanates. Mutat. Res., 300, 111-117.
43. Musk, S.R. et al. (1995) Cytotoxic and clastogenic effects of benzyl isothiocyanate towards cultured mammalian cells. Food Chem. Toxicol., 33, 31-37.
44. Kassie, F. et al. (1999) Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent. Mutagenesis, 14, 595-604.
45. Ding, Y. et al. (2010) Sulforaphane inhibits 4-aminobiphenyl-induced DNA damage in bladder cells and tissues. Carcinogenesis, 31, 1999-2003.
46. Munday, R. et al. (2008) Inhibition of urinary bladder carcinogenesis by broccoli sprouts. Cancer Res., 68, 1593-1600.
47. Khor, T.O. et al. (2008) Chemoprevention of familial adenomatous polyposis in ApcMin/+ mice by phenethyl isothiocyanate (PEITC). Mol. Carcinog., 47, 321-325.
48. McCune, K. et al. (2010) Loss of ERa and FOXA1 expression in a progression model of luminal type breast cancer: insights from PyMT transgenic mouse model. Oncol. Rep., 24, 1233-1239.
49. Barve, A. et al. (2008) Murine prostate cancer inhibition by dietary phytochemicals- curcumin and phenyethylisothiocyanate. Pharm. Res., 25, 2181-2189.
50. Powolny, A.A. et al. (2011) Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer. J. Natl. Cancer Inst., 103, 571-584.
51. Warin, R. et al. (2009) Prevention of mammary carcinogenesis in MMTV-neu mice by cruciferous vegetable constituent benzyl isothiocyanate. Cancer Res., 69, 9473-9480.
52. min mice. FASEB J., 20, 506-508.
53. Hu, R. et al. (2006) Cancer chemoprevention of intestinal polyposis in ApcMin/+ mice by sulforaphane, a natural product derived from cruciferous vegetable. Carcinogenesis, 27, 2038-2046.
54. Singh, S.V. et al. (2009) Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells. Cancer Res., 69, 2117-2125.
55. Keum, Y.S. et al. (2009) Pharmacokinetics and pharmacodynamics of broccoli sprouts on the suppression of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: implication of induction of Nrf2, HO-1 and apoptosis and the suppression of Akt-dependent kinase pathway. Pharm. Res., 26, 2324-2331.
56. Hasegawa, T. et al. (1993) Isothiocyanates inhibit cell cycle progression of HeLa cells at G2/M phase. Anticancer. Drugs, 4, 273-279.
57. 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.
58. Visanji, J.M. et al. (2004) Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase cell cycle arrest, DNA damage, and G2/M checkpoint activation. J. Nutr., 134, 3121-3126.
59. Jakubíková,J. et al. (2005) Effects of MEK1 and PI3K inhibitors on allyl-, benzyl- and phenylethyl-isothiocyanate-induced G2/M arrest and cell death in Caco-2 cells. Int. J. Oncol., 27, 1449-1458.
60. Miyoshi, N. et al. (2004) Benzyl isothiocyanate modifies expression of the G2/M arrest-related genes. Biofactors, 21, 23-26.
61. 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.
62. 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.
63. Zhang, Y. et al. (2003) Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol. Cancer Ther., 2, 1045-1052.
64. Wu, C.L. et al. (2011) Benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC)-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of caspase-3, mitochondria dysfunction and nitric oxide (NO) in human osteogenic sarcoma U-2 OS cells. J. Orthop. Res., 29, 1199-1209.
65. 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.
66. Jackson, S.J. et al. (2004) Sulforaphane: a naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization. Carcinogenesis, 25, 219-227.
67. 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.
68. Herman-Antosiewicz, A. et al. (2007) Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line. Mol. Cancer Ther., 6, 1673-1681.
69. Sakao, K. et al. (2012) Phenethyl isothiocyanate suppresses inhibitor of apoptosis family protein expression in prostate cancer cells in culture and in vivo. Prostate, 72, 1104-1116.
70. Choi, S. et al. (2005) Bax and Bak are required for apoptosis induction by sulforaphane, a cruciferous vegetable-derived cancer chemopreventive agent. Cancer Res., 65, 2035-2043.
71. Cheung, K.L. et al. (2010) Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J., 12, 87-97.
72. Yu, R. et al. (1998) Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity. Cancer Res., 58, 402-408.
73. Huang, C. et al. (1998) Essential role of p53 in phenethyl isothiocyanate-induced apoptosis. Cancer Res., 58, 4102-4106.
74. Xiao, D. et al. (2002) Phenethyl isothiocyanate-induced apoptosis in p53-deficient PC-3 human prostate cancer cell line is mediated by extracellular signal-regulated kinases. Cancer Res., 62, 3615-3619.
75. Kim, S.H. et al. (2010) p53-Independent apoptosis by benzyl isothiocyanate in human breast cancer cells is mediated by suppression of XIAP expression. Cancer Prev. Res., 3, 718-726.
76. Wang, X. et al. (2011) Selective depletion of mutant p53 by cancer chemopreventive isothiocyanates and their structure-activity relationships. J. Med. Chem., 54, 809-816.
77. Rose, P. et al. (2005) ß-phenylethyl isothiocyanate mediated apoptosis; contribution of Bax and the mitochondrial death pathway. Int. J. Biochem. Cell Biol., 37, 100-119.
78. Trachootham, D. et al. (2006) Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by ß-phenylethyl isothiocyanate. Cancer Cell, 10, 241-252.
79. Singh, S.V. et al. (2005) Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J. Biol. Chem., 280, 19911-19924.
80. Xiao, D. et al. (2008) Benzyl isothiocyanate targets mitochondrial respiratory chain to trigger reactive oxygen species-dependent apoptosis in human breast cancer cells. J. Biol. Chem., 283, 30151-30163.
81. Xiao, D. et al. (2010) Phenethyl isothiocyanate inhibits oxidative phosphorylation to trigger reactive oxygen species-mediated death of human prostate cancer cells. J. Biol. Chem., 285, 26558-26569.
82. Xiao, D. et al. (2009) Cellular responses to cancer chemopreventive agent D, L-sulforaphane in human prostate cancer cells are initiated by mitochondrial reactive oxygen species. Pharm. Res., 26, 1729-1738.
83. Powolny, A.A. et al. (2010) Differential response of normal (PrEC) and cancerous human prostate cells (PC-3) to phenethyl isothiocyanate-mediated changes in expression of antioxidant defense genes. Pharm. Res., 27, 2766-2775.
84. Shc is indispensable for phenethyl isothiocyanate-induced apoptosis in human prostate cancer cells. Cancer Res., 70, 3150-3158.
85. Shc. J. Cell. Biochem., 113, 599-610.
86. Folkman, J. (1971) Tumor angiogenesis: therapeutic implications. N. Engl. J. Med., 285, 1182-1186.
87. Xiao, D. et al. (2007) Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res., 67, 2239-2246.
88. Wang, X.H. et al. (2009) Inhibition of hypoxia inducible factor by phenethyl isothiocyanate. Biochem. Pharmacol., 78, 261-272.
89. Warin, R. et al. (2010) Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Mol. Carcinog., 49, 500-507.
90. Kim, E.J. et al. (2011) Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. Breast Cancer Res. Treat., 130, 61-71.
91. Boreddy, S.R. et al. (2011) Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-a/VEGF/ Rho-GTPases: pivotal role of STAT-3. PLoS ONE, 6, e25799.
92. 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.
93. Jackson, S.J. et al. (2007) Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Vascul. Pharmacol., 46, 77-84.
94. Cavell, B.E. et al. (2011) Anti-angiogenic effects of dietary isothiocyanates: mechanisms of action and implications for human health. Biochem. Pharmacol., 81, 327-336.
95. Dikic, I. et al. (2010) Selective autophagy in cancer development and therapy. Cancer Res., 70, 3431-3434.
96. Gibson, S.B. (2010) A matter of balance between life and death: targeting reactive oxygen species (ROS)-induced autophagy for cancer therapy. Autophagy, 6, 835-837.
97. Herman-Antosiewicz, A. et al. (2006) Sulforaphane causes autophagy to inhibit release of cytochrome c and apoptosis in human prostate cancer cells. Cancer Res., 66, 5828-5835.
98. Nishikawa, T. et al. (2010) Inhibition of autophagy potentiates sulforaphane-induced apoptosis in human colon cancer cells. Ann. Surg. Oncol., 17, 592-602.
99. Naumann, P. et al. (2011) Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer. Int. J. Oncol., 39, 101-109.
100. Bommareddy, A. et al. (2009) Atg5 regulates phenethyl isothiocyanate-induced autophagic and apoptotic cell death in human prostate cancer cells. Cancer Res., 69, 3704-3712.
101. Xiao, D. et al. (2012) Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells. PLoS ONE, 7, e32597.
102. Vinogradov, S. et al. (2012) Cancer stem cells and drug resistance: the potential of nanomedicine. Nanomedicine, 7, 597-615.
103. Alison, M.R. et al. (2012) Cancer stem cells: In the line of fire. Cancer Treat. Rev., 38, 589-598.
104. Li, Y. et al. (2010) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin. Cancer Res., 16, 2580-2590.
105. Sehrawat, A. et al. (2011) Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells. Cancer Prev. Res., 4, 1107-1117.
106. Thiery, J.P. (2002) Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer, 2, 442-454.
107. Chen, S.C. et al. (2012) Hepatoma-derived growth factor regulates breast cancer cell invasion by modulating epithelial mesenchymal transition. J. Pathol. Doi: 10.1002/path.3988.
108. 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.
109. Fimognari, C. et al. (2008) Chemoprevention of cancer by isothiocyanates and anthocyanins: mechanisms of action and structure-activity relationship. Curr. Med. Chem., 15, 440-447.
110. Juge, N. et al. (2007) Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell. Mol. Life Sci., 64, 1105-1127.
111. Dashwood, R.H. et al. (2008) Dietary agents as histone deacetylase inhibitors: sulforaphane and structurally related isothiocyanates. Nutr. Rev., 66 (Suppl. 1), S36-S38.
112. Xu, C. et al. (2005) Suppression of NF-κB and NF-κB-regulated gene expression by sulforaphane and PEITC through IκBa, IKK pathway in human prostate cancer PC-3 cells. Oncogene, 24, 4486-4495.
113. 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.
114. 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., 3, 484-494.
115. Kim, S.H. et al. (2009) D, L-Sulforaphane causes transcriptional repression of androgen receptor in human prostate cancer cells. Mol. Cancer Ther., 8, 1946-1954.
116. Kang, L. et al. (2009) Isothiocyanates repress estrogen receptor alpha expression in breast cancer cells. Oncol. Rep., 21, 185-192.
117. Mi, L. et al. (2011) Proteins as binding targets of isothiocyanates in cancer prevention. Carcinogenesis, 32, 1405-1413.
118. Hu, J. et al. (2007) 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, 3569-3573.
119. Hahm, E.R. et al. (2012) Bim contributes to phenethyl isothiocyanate-induced apoptosis in breast cancer cells. Mol. Carcinog., 51, 465-474.
120. Antony, M.L. et al. (2012) Critical role of p53 upregulated modulator of apoptosis in benzyl isothiocyanate-induced apoptotic cell death. PLoS ONE, 7, e32267.
121. Shannan, B. et al. (2006) Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer. Cell Death Differ., 13, 12-19.
122. Miyake, H. et al. (2006) Expression of clusterin in prostate cancer correlates with Gleason score but not with prognosis in patients undergoing radical prostatectomy without neoadjuvant hormonal therapy. Urology, 68, 609-614.
123. Kumar, A. et al. (2010) New biomarkers for monitoring the levels of isothiocyanates in humans. Chem. Res. Toxicol., 23, 756-765.
124. Kumar, A. et al. (2010) Determination of new biomarkers to monitor the dietary consumption of isothiocyanates. Biomarkers, 15, 739-745.
125. Pullar, J.M. et al. (2004) The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas-mediated apoptosis. Carcinogenesis, 25, 765-772.
126. Tseng, E. et al. (2002) Effect of organic isothiocyanates on the P-glycoprotein- and MRP1-mediated transport of daunomycin and vinblastine. Pham. Res., 19, 1509-1515.
127. Hu, K. et al. (2004) Effects of benzyl-, phenethyl-, and alpha-naphthyl isothiocyanates on P-glycoprotein- and MRP1-mediated transport. J. Pharm. Sci., 93, 1901-1911.
128. Mukherjee, S. et al. (2009) Targeting protein kinase C (PKC) and telomerase by phenethyl isothiocyanate (PEITC) sensitizes PC-3 cells towards chemotherapeutic drug-induced apoptosis. J. Environ. Pathol. Toxicol. Oncol., 28, 269-282.
129. Mukherjee, S. et al. (2009) Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells. Mol. Cell. Biochem., 330, 9-22.
130. Di Pasqua, A.J. et al. (2010) Sensitization of non-small cell lung cancer cells to cisplatin by naturally occurring isothiocyanates. Chem. Res. Toxicol., 23, 1307-1309.
131. Xiao, D. et al. (2010) Phenethyl isothiocyanate sensitizes androgen-independent human prostate cancer cells to docetaxel-induced apoptosis in vitro and in vivo. Pharm. Res., 27, 722-731.
132. Sahu, R.P. et al. (2009) Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy. Front. Biosci., 1, 568-576.
133. Ohara, M. et al. (2011) Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation by inducing apoptosis. Int. J. Mol. Med., 28, 1043-1047.
134. Wicker, C.A. et al. (2010) BITC sensitizes pancreatic adenocarcinomas to TRAIL-induced apoptosis. Cancer Growth Metastasis, 2, 45-55.
135. Kallifatidis, G. et al. (2011) Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol. Ther., 19, 188-195.
136. Ser220 mutation. Ann. N. Y. Acad. Sci., 1095, 62-69.
137. Kim, S.H. et al. (2011) Notch activation by phenethyl isothiocyanate attenuates its inhibitory effect on prostate cancer cell migration. PLoS ONE, 6, e26615.
138. Dang, T.P. (2012) Notch, apoptosis and cancer. Adv. Exp. Med. Biol., 727, 199-209.
139. Hu, Y.Y. et al. (2012) Notch signaling pathway and cancer metastasis. Adv. Exp. Med. Biol., 727, 186-198.
140. Wang, J. et al. (2012) Notch signaling in cancer stem cells. Adv. Exp. Med. Biol., 727, 174-185.
141. Kim, S.H. et al. (2012) Notch2 activation by benzyl isothiocyanate impedes its inhibitory effect on breast cancer cell migration. Breast Cancer Res. Treat. doi: 10.1007/S10549-012-2043-3.
142. Croce, C.M. (2009) Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet., 10, 704-714.
143. Basu, A. et al. (2011) MicroRNA-375 and MicroRNA-221: Potential Noncoding RNAs Associated with Antiproliferative Activity of Benzyl Isothiocyanate in pancreatic cancer. Genes Cancer, 2, 108-119.
144. Szafranska, A.E. et al. (2007) MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma. Oncogene, 26, 4442-4452.
145. Hecht, S.S. et al. (1995) Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers. Cancer Epidemiol. Biomarkers Prev., 4, 877-884.
146. Syed Alwi, S.S. et al. (2010) In vivo modulation of 4E binding protein 1 (4E-BP1) phosphorylation by watercress: a pilot study. Br. J. Nutr., 104, 1288-1296.
147. Shapiro, T.A. et al. (2006) Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase 1 study. Nutr. Cancer, 55, 53-62.
148. Kensler, T.W. et al. (2005) Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China. Cancer Epidemiol. Biomarkers Prev., 14, 2605-2613.
149. Myzak, M.C. et al. (2007) Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp. Biol. Med., 232, 227-234.