Molecular targets of isothiocyanates in cancer: Recent advances

Molecular Nutrition and Food Research

Volumn 58, Issue 8, 2014, Pages 1685-1707

  Gupta, Parul ^a   Kim, Bonglee ^b   Kim, Sung Hoon ^b   Srivastava, Sanjay K ^a,b  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b Kyung Hee University   (South Korea)

Author keywords

BITC; Cancer; Isothiocyanate; PEITC; Sulforaphane

Indexed keywords

ANTINEOPLASTIC AGENT; ISOTHIOCYANIC ACID DERIVATIVE;

ANIMAL; BIOLOGICAL MODEL; DIET SUPPLEMENTATION; DIET THERAPY; HUMAN; MEDICAL RESEARCH; NEOPLASMS; TRENDS;

ANIMALS; ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; BIOMEDICAL RESEARCH; DIETARY SUPPLEMENTS; HUMANS; ISOTHIOCYANATES; MODELS, BIOLOGICAL; NEOPLASMS;

EID: 84904649739     PISSN: 16134125     EISSN: 16134133     Source Type: Journal    
DOI: 10.1002/mnfr.201300684     Document Type: Article

References (214)

1. Newman, D. J., Cragg, G. M., Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 2012, 75, 311-335.
2. Higdon, J. V., Delage, B., Williams, D. E., Dashwood, R. H., Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol. Res. 2007, 55, 224-236.
3. Boggs, D. A., Palmer, J. R., Wise, L. A., Spiegelman, D. et al., Fruit and vegetable intake in relation to risk of breast cancer in the Black Women's Health Study. Am. J. Epidemiol. 2010, 172, 1268-1279.
4. Block, G., Patterson, B., Subar, A., Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr. Cancer 1992, 18, 1-29.
5. Tang, L., Zirpoli, G. R., Guru, K., Moysich, K. B. et al., Intake of cruciferous vegetables modifies bladder cancer survival. Cancer Epidemiol. Biomarkers Prev. 2010, 19, 1806-1811.
6. Palmer, S., Diet, nutrition, and cancer. Prog. Food Nutr. Sci. 1985, 9, 283-341.
7. Boreddy, S. R., Srivastava, S. K., Pancreatic cancer chemoprevention by phytochemicals. Cancer Lett. 2012, 86-94.
8. Fowke, J. H., Chung, F. L., Jin, F., Qi, D. et al., Urinary isothiocyanate levels, Brassica, and human breast cancer. Cancer Res. 2003, 63, 3980-3986.
9. Ambrosone, C. B., McCann, S. E., Freudenheim, J. L., Marshall, J. R. et al., Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J. Nutr. 2004, 134, 1134-1138.
10. Bosetti, C., Negri, E., Franceschi, S., Pelucchi, C. et al., Diet and ovarian cancer risk: a case-control study in Italy. Int. J. Cancer 2001, 93, 911-915.
11. Zhang, M., Yang, Z. Y., Binns, C. W., Lee, A. H., Diet and ovarian cancer risk: a case-control study in China. Br J. Cancer 2002, 86, 712-717.
12. Shapiro, T. A., Fahey, J. W., Wade, K. L., Stephenson, K. K. et al., Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol. Biomarkers Prev. 2001, 10, 501-508.
13. Stoner, G. D., Morse, M. A., Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer. Cancer Lett. 1997, 114, 113-119.
14. Zhang, Y., Talalay, P., Cho, C. G., Posner, G. H., A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl. Acad. Sci. USA 1992, 89, 2399-2403.
15. Fimognari, C., Lenzi, M., Hrelia, P., Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr. Drug Metab. 2008, 9, 668-678.
16. Gross-Steinmeyer, K., Stapleton, P. L., Liu, F., Tracy, J. H. et al., Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. Xenobiotica 2004, 34, 619-632.
17. Nakajima, M., Yoshida, R., Shimada, N., Yamazaki, H. et al., Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Drug Metab. Dispos. 2001, 29, 1110-1113.
18. Yoshigae, Y., Sridar, C., Kent, U. M., Hollenberg, P. F., The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation. Drug Metab. Dispos. 2013, 41, 858-869.
19. Morse, M. A., Amin, S. G., Hecht, S. S., Chung, F. L., Effects of aromatic isothiocyanates on tumorigenicity, O6-methylguanine formation, and metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung. Cancer Res. 1989, 49, 2894-2897.
20. Wattenberg, L. W., Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds. J. Natl. Cancer Inst. 1977, 58, 395-398.
21. Adam-Rodwell, G., Morse, M. A., Stoner, G. D., The effects of phenethyl isothiocyanate on benzo[a]pyrene-induced tumors and DNA adducts in A/J mouse lung. Cancer Lett. 1993, 71, 35-42.
22. Conaway, C. C., Wang, C. X., Pittman, B., Yang, Y. M. et al., 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. 2005, 65, 8548-8557.
23. Hecht, S. S., Approaches to chemoprevention of lung cancer based on carcinogens in tobacco smoke. Environ. Health Perspect. 1997, 105 (Suppl 4), 955-963.
24. Morse, M. A., Wang, C. X., Amin, S. G., Hecht, S. S. et al., Effects of dietary sinigrin or indole-3-carbinol on O6-methylguanine-DNA-transmethylase activity and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA methylation and tumorigenicity in F344 rats. Carcinogenesis 1988, 9, 1891-1895.
25. Munday, R., Munday, C. M., Induction of phase II detoxification enzymes in rats by plant-derived isothiocyanates: comparison of allyl isothiocyanate with sulforaphane and related compounds. J. Agric. Food Chem. 2004, 52, 1867-1871.
26. Jiao, D., Conaway, C. C., Wang, M. H., Yang, C. S. et al., Inhibition of N-nitrosodimethylamine demethylase in rat and human liver microsomes by isothiocyanates and their glutathione, L-cysteine, and N-acetyl-L-cysteine conjugates. Chem. Res. Toxicol. 1996, 9, 932-938.
27. Moreno, R. L., Kent, U. M., Hodge, K., Hollenberg, P. F., Inactivation of cytochrome P450 2E1 by benzyl isothiocyanate. Chem. Res. Toxicol. 1999, 12, 582-587.
28. Steinkellner, H., Rabot, S., Freywald, C., Nobis, E. et al., Effects of cruciferous vegetables and their constituents on drug metabolizing enzymes involved in the bioactivation of DNA-reactive dietary carcinogens. Mutat. Res. 2001, 480-481, 285-297.
29. Zhou, C., Poulton, E. J., Grun, F., Bammler, T. K. et al., The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor. Mol. Pharmacol. 2007, 71, 220-229.
30. Cheung, K. L., Kong, A. N., Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J. 2010, 12, 87-97.
31. Brooks, J. D., Paton, V. G., Vidanes, G., Potent induction of phase 2 enzymes in human prostate cells by sulforaphane. Cancer Epidemiol. Biomarkers Prev. 2001, 10, 949-954.
32. Talalay, P., Fahey, J. W., Holtzclaw, W. D., Prestera, T. et al., Chemoprotection against cancer by phase 2 enzyme induction. Toxicol. Lett. 1995, 82-83, 173-179.
33. Zhang, Y., Talalay, P., Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms. Cancer Res. 1994, 54, 1976s-1981s.
34. Hecht, S. S., Inhibition of carcinogenesis by isothiocyanates. Drug Metab. Rev. 2000, 32, 395-411.
35. Mannervik, B., The isoenzymes of glutathione transferase. Adv. Enzymol. Relat. Areas Mol. Biol. 1985, 57, 357-417.
36. Hayes, J. D., Pulford, D. J., The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 1995, 30, 445-600.
37. Thornalley, P. J., Isothiocyanates: mechanism of cancer chemopreventive action. Anticancer Drugs 2002, 13, 331-338.
38. Zhang, Y., Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells. Carcinogenesis 2000, 21, 1175-1182.
39. Beklemisheva, A. A., Feng, J., Yeh, Y. A., Wang, L. G. et al., Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 and androgen receptor down-regulation. Prostate 2007, 67, 863-870.
40. Wang, L. G., Chiao, J. W., Prostate cancer chemopreventive activity of phenethyl isothiocyanate through epigenetic regulation (review). Int. J. Oncol. 2010, 37, 533-539.
41. Kong, A. N., Yu, R., Hebbar, V., Chen, C. et al., Signal transduction events elicited by cancer prevention compounds. Mutat. Res. 2001, 480-481, 231-241.
42. Keum, Y. S., Yu, S., Chang, P. P., Yuan, X. et al., Mechanism of action of sulforaphane: inhibition of p38 mitogen-activated protein kinase isoforms contributing to the induction of antioxidant response element-mediated heme oxygenase-1 in human hepatoma HepG2 cells. Cancer Res. 2006, 66, 8804-8813.
43. Prawan, A., Keum, Y. S., Khor, T. O., Yu, S. et al., Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression. Pharm. Res. 2008, 25, 836-844.
44. Keum, Y. S., Jeong, W. S., Kong, A. N., Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms. Mutat. Res. 2004, 555, 191-202.
45. Zhang, C., Su, Z. Y., Khor, T. O., Shu, L. et al., Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation. Biochem. Pharmacol. 2013, 85, 1398-1404.
46. Fimognari, C., Hrelia, P., Sulforaphane as a promising molecule for fighting cancer. Mutat. Res. 2007, 635, 90-104.
47. Brigelius-Flohe, R., Banning, A., Part of the series: from dietary antioxidants to regulators in cellular signaling and gene regulation. Sulforaphane and selenium, partners in adaptive response and prevention of cancer. Free Radic. Res. 2006, 40, 775-787.
48. Bacon, J. R., Plumb, G. W., Howie, A. F., Beckett, G. J. et al., Dual action of sulforaphane in the regulation of thioredoxin reductase and thioredoxin in human HepG2 and Caco-2 cells. J. Agric. Food Chem. 2007, 55, 1170-1176.
49. Zhang, J., Svehlikova, V., Bao, Y., Howie, A. F. et al., Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation. Carcinogenesis 2003, 24, 497-503.
50. Wang, W., Wang, S., Howie, A. F., Beckett, G. J. et al., Sulforaphane, erucin, and iberin up-regulate thioredoxin reductase 1 expression in human MCF-7 cells. J. Agric. Food Chem. 2005, 53, 1417-1421.
51. Jakubikova, J., Cervi, D., Ooi, M., Kim, K. et al., Anti-tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma. Haematologica 2011, 96, 1170-1179.
52. Huang, C., Ma, W. Y., Li, J., Hecht, S. S. et al., Essential role of p53 in phenethyl isothiocyanate-induced apoptosis. Cancer Res. 1998, 58, 4102-4106.
53. Yu, R., Mandlekar, S., Harvey, K. J., Ucker, D. S. et al., Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity. Cancer Res. 1998, 58, 402-408.
54. Zhang, Y., Callaway, E. C., High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem. J. 2002, 364, 301-307.
55. Boreddy, S. R., Pramanik, K. C., Srivastava, S. K., Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway. Clin. Cancer Res. 2011, 17, 1784-1795.
56. Batra, S., Sahu, R. P., Kandala, P. K., Srivastava, S. K., Benzyl isothiocyanate-mediated inhibition of histone deacetylase leads to NF-kappaB turnoff in human pancreatic carcinoma cells. Mol. Cancer Ther. 2010, 9, 1596-1608.
57. Sahu, R. P., Zhang, R., Batra, S., Shi, Y. et al., Benzyl isothiocyanate-mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of MAPK in human pancreatic cancer cells. Carcinogenesis 2009, 30, 1744-1753.
58. Sahu, R. P., Epperly, M. W., Srivastava, S. K., Benzyl isothiocyanate sensitizes human pancreatic cancer cells to radiation therapy. Front. Biosci. 2009, 1, 568-576.
59. Sahu, R. P., Srivastava, S. K., The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. J. Natl. Cancer Inst. 2009, 101, 176-193.
60. Zhang, R., Loganathan, S., Humphreys, I., Srivastava, S. K., Benzyl isothiocyanate-induced DNA damage causes G2/M cell cycle arrest and apoptosis in human pancreatic cancer cells. J. Nutr. 2006, 136, 2728-2734.
61. Srivastava, S. K., Singh, S. V., 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 2004, 25, 1701-1709.
62. Kalkunte, S., Swamy, N., Dizon, D. S., Brard, L., Benzyl isothiocyanate (BITC) induces apoptosis in ovarian cancer cells in vitro. J. Exp. Ther. Oncol. 2006, 5, 287-300.
63. Nakamura, Y., Kawakami, M., Yoshihiro, A., Miyoshi, N. et al., Involvement of the mitochondrial death pathway in chemopreventive benzyl isothiocyanate-induced apoptosis. J. Biol. Chem. 2002, 277, 8492-8499.
64. Finkielsztein, A., Kelly, G. M., Altering PI3K-Akt signalling in zebrafish embryos affects PTEN phosphorylation and gastrulation. Biol. Cell 2009, 101, 661-678.
65. Schlieman, M. G., Fahy, B. N., Ramsamooj, R., Beckett, L. et al., Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br. J. Cancer 2003, 89, 2110-2115.
66. Sarbassov, D. D., Guertin, D. A., Ali, S. M., Sabatini, D. M., Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005, 307, 1098-1101.
67. Lin, J. F., Tsai, T. F., Liao, P. C., Lin, Y. H. et al., Benzyl isothiocyanate induces protective autophagy in human prostate cancer cells via inhibition of mTOR signaling. Carcinogenesis 2013, 34, 406-414.
68. Xiao, D., Bommareddy, A., Kim, S. H., Sehrawat, A. et al., Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells. PLoS One 2012, 7, e32597.
69. Ghosh, S., May, M. J., Kopp, E. B., NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 1998, 16, 225-260.
70. Sun, Z., Andersson, R., NF-kappaB activation and inhibition: a review. Shock 2002, 18, 99-106.
71. Darnell, J. E., Validating Stat3 in cancer therapy. Nat. Med. 2005, 11, 595-596.
72. Wei, D., Le, X., Zheng, L., Wang, L. et al., Stat3 activation regulates the expression of vascular endothelial growth factor and human pancreatic cancer angiogenesis and metastasis. Oncogene 2003, 22, 319-329.
73. Fouse, S. D., Costello, J. F., Cancer stem cells activate STAT3 the EZ way. Cancer Cell 2013, 23, 711-713.
74. Semenza, G. L., HIF-1 and mechanisms of hypoxia sensing. Curr. Opin. Cell Biol. 2001, 13, 167-171.
75. Xu, Q., Briggs, J., Park, S., Niu, G. et al., Targeting Stat3 blocks both HIF-1 and VEGF expression induced by multiple oncogenic growth signaling pathways. Oncogene 2005, 24, 5552-5560.
76. Jung, J. E., Lee, H. G., Cho, I. H., Chung, D. H. et al., STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J. 2005, 19, 1296-1298.
77. Boreddy, S. R., Sahu, R. P., Srivastava, S. K., Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-alpha/VEGF/Rho-GTPases: pivotal role of STAT-3. PLoS One 2011, 6, e25799.
78. Warin, R., Xiao, D., Arlotti, J. A., Bommareddy, A. et al., Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Mol. Carcinog. 2010, 49, 500-507.
79. Wu, C. L., Huang, A. C., Yang, J. S., Liao, C. L. et al., 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. 2011, 29, 1199-1209.
80. Wu, X., Zhu, Y., Yan, H., Liu, B. et al., Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells. BMC Cancer 2010, 10, 269.
81. Miyoshi, N., Takabayashi, S., Osawa, T., Nakamura, Y., Benzyl isothiocyanate inhibits excessive superoxide generation in inflammatory leukocytes: implication for prevention against inflammation-related carcinogenesis. Carcinogenesis 2004, 25, 567-575.
82. Zhu, Y., Zhuang, J. X., Wang, Q., Zhang, H. Y. et al., Inhibitory effect of benzyl isothiocyanate on proliferation in vitro of human glioma cells. Asian Pac. J. Cancer Prev. 2013, 14, 2607-2610.
83. Kawakami, M., Harada, N., Hiratsuka, M., Kawai, K. et al., Dietary isothiocyanates modify mitochondrial functions through their electrophilic reaction. Biosci. Biotechnol. Biochem. 2005, 69, 2439-2444.
84. Zhou, T., Li, G., Cao, B., Liu, L. et al., Downregulation of Mcl-1 through inhibition of translation contributes to benzyl isothiocyanate-induced cell cycle arrest and apoptosis in human leukemia cells. Cell Death Dis. 2013, 4, e515.
85. Kim, E. J., Hong, J. E., Eom, S. J., Lee, J. Y. et al., 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. 2011, 130, 61-71.
86. Sehrawat, A., Kim, S. H., Vogt, A., Singh, S. V., Suppression of FOXQ1 in benzyl isothiocyanate-mediated inhibition of epithelial-mesenchymal transition in human breast cancer cells. Carcinogenesis 2013, 34, 864-873.
87. Kim, S. H., Sehrawat, A., Singh, S. V., Dietary chemopreventative benzyl isothiocyanate inhibits breast cancer stem cells in vitro and in vivo. Cancer Prev. Res. 2013, 6, 782-790.
88. Kim, S. H., Sehrawat, A., Singh, S. V., Notch2 activation by benzyl isothiocyanate impedes its inhibitory effect on breast cancer cell migration. Breast Cancer Res. Treat. 2012, 134, 1067-1079.
89. Qhattal, H. S., Wang, S., Salihima, T., Srivastava, S. K. et al., Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability. J. Agric. Food Chem. 2011, 59, 12396-12404.
90. Lewerenz, H. J., Bleyl, D. W., Plass, R., Subacute oral toxicity study of benzyl isothiocyanate in rats. Die Nahrung 1992, 36, 190-198.
91. Hecht, S. S., Chung, F. L., Richie, J. P. Jr., Akerkar, S. A. et al., Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers. Cancer Epidemiol. Biomarkers Prev. 1995, 4, 877-884.
92. Chung, F. L., Morse, M. A., Eklind, K. I., Lewis, J., Quantitation of human uptake of the anticarcinogen phenethyl isothiocyanate after a watercress meal. Cancer Epidemiol. Biomarkers Prev. 1992, 1, 383-388.
93. Guo, Z., Smith, T. J., Wang, E., Eklind, K. I. et al., Structure-activity relationships of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism and the modulation of xenobiotic-metabolizing enzymes in rats and mice. Carcinogenesis 1993, 14, 1167-1173.
94. Gupta, P., Adkins, C., Lockman, P., Srivastava, S., Metastasis of breast tumor cells to brain is suppressed by phenethyl isothiocyanate in a novel in vivo metastasis model. PLoS One 2013, 8, e67278.
95. Gupta, P., Srivastava, S. K., Antitumor activity of phenethyl isothiocyanate in HER2-positive breast cancer models. BMC Med. 2012, 10, 80.
96. Trachootham, D., Zhou, Y., Zhang, H., Demizu, Y. et al., Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell 2006, 10, 241-252.
97. Xiao, D., Singh, S. V., Phenethyl isothiocyanate sensitizes androgen-independent human prostate cancer cells to docetaxel-induced apoptosis in vitro and in vivo. Pharm. Res. 2010, 27, 722-731.
98. Chen, G., Chen, Z., Hu, Y., Huang, P., Inhibition of mitochondrial respiration and rapid depletion of mitochondrial glutathione by beta-phenethyl isothiocyanate: mechanisms for anti-leukemia activity. Antioxid. Redox Signal. 2011, 15, 2911-2921.
99. Syed Alwi, S. S., Cavell, B. E., Donlevy, A., Packham, G., Differential induction of apoptosis in human breast cancer cell lines by phenethyl isothiocyanate, a glutathione depleting agent. Cell Stress Chaperones 2012, 17, 529-538.
100. Powolny, A. A., Singh, S. V., 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. 2010, 27, 2766-2775.
101. Chen, Y. R., Wang, W., Kong, A. N., Tan, T. H., Molecular mechanisms of c-Jun N-terminal kinase-mediated apoptosis induced by anticarcinogenic isothiocyanates. J. Biol. Chem. 1998, 273, 1769-1775.
102. Yang, Y. M., Conaway, C. C., Chiao, J. W., Wang, C. X. et al., 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. 2002, 62, 2-7.
103. Lai, K. C., Hsu, S. C., Kuo, C. L., Ip, S. W. et al., Phenethyl isothiocyanate inhibited tumor migration and invasion via suppressing multiple signal transduction pathways in human colon cancer HT29 cells. J. Agric. Food Chem. 2010, 11148-11155.
104. Hwang, E. S., Lee, H. J., Phenylethyl isothiocyanate and its N-acetylcysteine conjugate suppress the metastasis of SK-Hep1 human hepatoma cells. J. Nutr. Biochem. 2006, 17, 837-846.
105. Xiao, D., Singh, S. V., Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res. 2007, 67, 2239-2246.
106. Wang, X. H., Cavell, B. E., Syed Alwi, S. S., Packham, G., Inhibition of hypoxia inducible factor by phenethyl isothiocyanate. Biochem. Pharmacol. 2009, 78, 261-272.
107. Mi, L., Hood, B. L., Stewart, N. A., Xiao, Z. et al., Identification of potential protein targets of isothiocyanates by proteomics. Chem. Res. Toxicol. 2011, 24, 1735-1743.
108. Suzuki, S., Dobashi, Y., Minato, H., Tajiri, R. et al., EGFR and HER2-Akt-mTOR signaling pathways are activated in subgroups of salivary gland carcinomas. Virchows Arch. 2012, 461, 271-282.
109. Loganathan, S., Kandala, P. K., Gupta, P., Srivastava, S. K., Inhibition of EGFR-AKT axis results in the suppression of ovarian tumors in vitro and in preclinical mouse model. PLoS One 2012, 7, e43577.
110. Kang, L., Wang, Z. Y., Breast cancer cell growth inhibition by phenethyl isothiocyanate is associated with down-regulation of oestrogen receptor-alpha36. J. Cell. Mol. Med. 2010, 14, 1485-1493.
111. Syed Alwi, S. S., Cavell, B. E., Telang, U., Morris, M. E. et al., In vivo modulation of 4E binding protein 1 (4E-BP1) phosphorylation by watercress: a pilot study. Br. J. Nutr. 2010, 104, 1288-1296.
112. Izzotti, A., Larghero, P., Balansky, R., Pfeffer, U. et al., Interplay between histopathological alterations, cigarette smoke and chemopreventive agents in defining microRNA profiles in mouse lung. Mutat. Res. 2011, 717, 17-24.
113. Huong, L. D., Shin, J. A., Choi, E. S., Cho, N. P. et al., Beta-phenethyl isothiocyanate induces death receptor 5 to induce apoptosis in human oral cancer cells via p38. Oral Dis. 2012, 18, 513-519.
114. Huong le, D., Shim, J. H., Choi, K. H., Shin, J. A. et al., Effect of beta-phenylethyl isothiocyanate from cruciferous vegetables on growth inhibition and apoptosis of cervical cancer cells through the induction of death receptors 4 and 5. J. Agric. Food Chem. 2011, 59, 8124-8131.
115. Pullar, J. M., Thomson, S. J., King, M. J., Turnbull, C. I. et al., The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas-mediated apoptosis. Carcinogenesis 2004, 25, 765-772.
116. Chen, P. Y., Lin, K. C., Lin, J. P., Tang, N. Y. et al., Phenethyl isothiocyanate (PEITC) inhibits the growth of human oral squamous carcinoma HSC-3 cells through G(0)/G(1) phase arrest and mitochondria-mediated apoptotic cell death. Evid. Based Complement. Altern. Med. 2012, 2012, 718320.
117. Tang, N. Y., Huang, Y. T., Yu, C. S., Ko, Y. C. et al., Phenethyl isothiocyanate (PEITC) promotes G2/M phase arrest via p53 expression and induces apoptosis through caspase- and mitochondria-dependent signaling pathways in human prostate cancer DU 145 cells. Anticancer Res. 2011, 31, 1691-1702.
118. Lee, J. W., Cho, M. K., Phenethyl isothiocyanate induced apoptosis via down regulation of Bcl-2/XIAP and triggering of the mitochondrial pathway in MCF-7 cells. Arch. Pharm. Res. 2008, 31, 1604-1612.
119. Xiao, D., Lew, K. L., Zeng, Y., Xiao, H. et al., Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential. Carcinogenesis 2006, 27, 2223-2234.
120. Wang, X., Di Pasqua, A. J., Govind, S., McCracken, E. et al., Selective depletion of mutant p53 by cancer chemopreventive isothiocyanates and their structure-activity relationships. J. Med. Chem. 2011, 54, 809-816.
121. Chiao, J. W., Wu, H., Ramaswamy, G., Conaway, C. C. et al., Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis 2004, 25, 1403-1408.
122. Saw, C. L., Cintron, M., Wu, T. Y., Guo, Y. et al., Pharmacodynamics of dietary phytochemical indoles I3C and DIM: induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates. Biopharm. Drug Dispos. 2011, 32, 289-300.
123. Moon, Y. J., Brazeau, D. A., Morris, M. E., Dietary phenethyl isothiocyanate alters gene expression in human breast cancer cells. Evid. Based Complement. Altern. Med. 2011, 2011, 462525.
124. Pawlik, A., Szczepanski, M. A., Klimaszewska, A., Gackowska, L. et al., Phenethyl isothiocyanate-induced cytoskeletal changes and cell death in lung cancer cells. Food Chem. Toxicol. 2012, 50, 3577-3594.
125. Sakao, K., Desineni, S., Hahm, E. R., Singh, S. V., Phenethyl isothiocyanate suppresses inhibitor of apoptosis family protein expression in prostate cancer cells in culture and in vivo. Prostate 2012, 72, 1104-1116.
126. Ji, Y., Kuo, Y., Morris, M. E., Pharmacokinetics of dietary phenethyl isothiocyanate in rats. Pharm. Res. 2005, 22, 1658-1666.
127. Conaway, C. C., Jiao, D., Kohri, T., Liebes, L. et al., Disposition and pharmacokinetics of phenethyl isothiocyanate and 6-phenylhexyl isothiocyanate in F344 rats. Drug Metab. Dispos. 1999, 27, 13-20.
128. Gao, N., Budhraja, A., Cheng, S., Liu, E. H. et al., Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways. Cell Death Dis. 2011, 2, e140.
129. Tsou, M. F., Tien, N., Lu, C. C., Chiang, J. H. et al., Phenethyl isothiocyanate promotes immune responses in normal BALB/c mice, inhibits murine leukemia WEHI-3 cells, and stimulates immunomodulations in vivo. Environ. Toxicol. 2013, 28, 127-136.
130. Li, Y., Wang, E. J., Chen, L., Stein, A. P. et al., Effects of phenethyl isothiocyanate on acetaminophen metabolism and hepatotoxicity in mice. Toxicol. Appl. Pharmacol. 1997, 144, 306-314.
131. Mi, L., Xiao, Z., Hood, B. L., Dakshanamurthy, S. et al., Covalent binding to tubulin by isothiocyanates. A mechanism of cell growth arrest and apoptosis. J. Biol. Chem. 2008, 283, 22136-22146.
132. Myzak, M. C., Hardin, K., Wang, R., Dashwood, R. H. et al., Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis 2006, 27, 811-819.
133. Dashwood, R. H., Ho, E., Dietary histone deacetylase inhibitors: from cells to mice to man. Semin. Cancer Biol. 2007, 17, 363-369.
134. 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, 374-380.
135. Xu, C., Shen, G., Chen, C., Gelinas, C. et al., 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 2005, 24, 4486-4495.
136. Pledgie-Tracy, A., Sobolewski, M. D., Davidson, N. E., Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol. Cancer Ther. 2007, 6, 1013-1021.
137. Rajendran, P., Kidane, A. I., Yu, T. W., Dashwood, W. M. et al., HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates. Epigenetics 2013, 8, 612-623.
138. Hsu, A., Wong, C. P., Yu, Z., Williams, D. E. et al., Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells. Clin. Epigenetics 2011, 3, 3.
139. Jackson, S. J., Singletary, K. W., Venema, R. C., Sulforaphane suppresses angiogenesis and disrupts endothelial mitotic progression and microtubule polymerization. Vasc. Pharmacol. 2007, 46, 77-84.
140. Bertl, E., Bartsch, H., Gerhauser, C., Inhibition of angiogenesis and endothelial cell functions are novel sulforaphane-mediated mechanisms in chemoprevention. Mol. Cancer Ther. 2006, 5, 575-585.
141. Davis, R., Singh, K. P., Kurzrock, R., Shankar, S., Sulforaphane inhibits angiogenesis through activation of FOXO transcription factors. Oncol. Rep. 2009, 22, 1473-1478.
142. Choi, S., Lew, K. L., Xiao, H., Herman-Antosiewicz, A. et al., D, L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1. Carcinogenesis 2007, 28, 151-162.
143. Li, S. H., Fu, J., Watkins, D. N., Srivastava, R. K. et al., Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of Sonic hedgehog-GLI pathway. Mol. Cell. Biochem. 2013, 373, 217-227.
144. Singh, S. V., Srivastava, S. K., Choi, S., Lew, K. L. et al., Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J. Biol. Chem. 2005, 280, 19911-19924.
145. Hsu, Y. C., Chang, S. J., Wang, M. Y., Chen, Y. L. et al., Growth inhibition and apoptosis of neuroblastoma cells through ROS-independent MEK/ERK activation by sulforaphane. Cell Biochem. Biophys. 2013, 66, 765-774.
146. Shan, Y., Sun, C., Zhao, X., Wu, K. 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, 883-888.
147. Gamet-Payrastre, L., Li, P., Lumeau, S., Cassar, G. et al., Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 2000, 60, 1426-1433.
148. Suppipat, K., Park, C. S., Shen, Y., Zhu, X. et al., Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells. PLoS One 2012, 7, e51251.
149. Shen, G., Xu, C., Chen, C., Hebbar, V. et al., p53-independent G1 cell cycle arrest of human colon carcinoma cells HT-29 by sulforaphane is associated with induction of p21CIP1 and inhibition of expression of cyclin D1. Cancer Chemother. Pharmacol. 2006, 57, 317-327.
150. Jakubikova, J., Sedlak, J., Mithen, R., Bao, Y., Role of PI3K/Akt and MEK/ERK signaling pathways in sulforaphane- and erucin-induced phase II enzymes and MRP2 transcription, G2/M arrest and cell death in Caco-2 cells. Biochem. Pharmacol. 2005, 69, 1543-1552.
151. Jee, H. G., Lee, K. E., Kim, J. B., Shin, H. K. et al., Sulforaphane inhibits oral carcinoma cell migration and invasion in vitro. Phytother. Res. 2011, 25, 1623-1628.
152. Kanematsu, S., Yoshizawa, K., Uehara, N., Miki, H. 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, 603-608.
153. Shan, Y., Zhang, L., Bao, Y., Li, B. et al., Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells. J. Nutr. Biochem. 2013, 24, 1062-1069.
154. Gerhauser, C., Epigenetic impact of dietary isothiocyanates in cancer chemoprevention. Curr. Opin. Clin. Nutr. Metab. Care 2013, 16, 405-410.
155. Hu, R., Hebbar, V., Kim, B. R., Chen, C. et al., In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat. J. Pharmacol. Exp. Ther. 2004, 310, 263-271.
156. Cornblatt, B. S., Ye, L., Dinkova-Kostova, A. T., Erb, M. et al., Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis 2007, 28, 1485-1490.
157. Hu, R., Khor, T. O., Shen, G., Jeong, W. S. et al., Cancer chemoprevention of intestinal polyposis in ApcMin/ +mice by sulforaphane, a natural product derived from cruciferous vegetable. Carcinogenesis 2006, 27, 2038-2046.
158. Priya, D. K. D., Gayathri, R., Gunassekaran, G. R., Murugan, S. et al., Inhibitory effect of sulforaphane against benzo(a)pyrene induced lung cancer by modulation of biochemical signatures in female Swiss albino mice. Asian J. Biochem. 2011, 6, 395-405.
159. Zhao, H. D., Zhang, F., Shen, G., Li, Y. B. et al., Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway. World J. Gastroenterol. 2010, 16, 3002-3010.
160. Jiao, D., Ho, C. T., Foiles, P., Chung, F. L., Identification and quantification of the N-acetylcysteine conjugate of allyl isothiocyanate in human urine after ingestion of mustard. Cancer Epidemiol. Biomarkers Prev. 1994, 3, 487-492.
161. Charron, C. S., Clevidence, B. A., Albaugh, G. A., Kramer, M. H. et al., Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables. J. Nutr. Biochem. 2013, 24, 894-902.
162. Smith, T., Musk, S. R., Johnson, I. T., Allyl isothiocyanate selectively kills undifferentiated HT29 cells in vitro and suppresses aberrant crypt foci in the colonic mucosa of rats. Biochem. Soc. Trans. 1996, 24, 381S.
163. Smith, T. K., Lund, E. K., Parker, M. L., Clarke, R. G. et al., Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells. Carcinogenesis 2004, 25, 1409-1415.
164. Xu, C., Shen, G., Yuan, X., Kim, J. H. et al., 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 2006, 27, 437-445.
165. Tsai, S. C., Huang, W. W., Huang, W. C., Lu, C. C. et al., ERK-modulated intrinsic signaling and G(2)/M phase arrest contribute to the induction of apoptotic death by allyl isothiocyanate in MDA-MB-468 human breast adenocarcinoma cells. Int. J. Oncol. 2012, 41, 2065-2072.
166. Geng, F., Tang, L., Li, Y., Yang, L. 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, 32259-32267.
167. Srivastava, S. K., Xiao, D., Lew, K. L., Hershberger, P. et al., Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. Carcinogenesis 2003, 24, 1665-1670.
168. Hwang, E. S., Lee, H. J., 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. 2006, 231, 421-430.
169. Kumar, A., D'Souza, S. S., Tickoo, S., Salimath, B. P. et al., Antiangiogenic and proapoptotic activities of allyl isothiocyanate inhibit ascites tumor growth in vivo. Integr. Cancer Ther. 2009, 8, 75-87.
170. Thejass, P., Kuttan, G., 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 2007, 16, 247-257.
171. Imaizumi, K., Sato, S., Sakakibara, Y., Mori, S. et al., Allyl isothiocyanate-induced changes in the distribution of white blood cells in rats. J. Toxicol. Sci. 2010, 35, 583-589.
172. Manesh, C., Kuttan, G., Effect of naturally occurring isothiocyanates on the immune system. Immunopharmacol. Immunotoxicol. 2003, 25, 451-459.
173. Lewerenz, H. J., Plass, R., Macholz, R., Effect of allyl isothiocyanate on hepatic monooxygenases and serum transferases in rats. Toxicol. Lett. 1988, 44, 65-70.
174. Masutomi, N., Toyoda, K., Shibutani, M., Niho, N. et al., Toxic effects of benzyl and allyl isothiocyanates and benzyl-isoform specific metabolites in the urinary bladder after a single intravesical application to rats. Toxicol. Pathol. 2001, 29, 617-622.
175. Sawai, Y., Murata, H., Horii, M., Koto, K. et al., Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells. Oncol. Rep. 2013, 29, 941-945.
176. Wu, W. J., Zhang, Y., Zeng, Z. L., Li, X. B. et al., beta-phenylethyl isothiocyanate reverses platinum resistance by a GSH-dependent mechanism in cancer cells with epithelial-mesenchymal transition phenotype. Biochem. Pharmacol. 2013, 85, 486-496.
177. Chan, D. K., Miskimins, W. K., Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures. J. Ovarian Res. 2012, 5, 19.
178. Hu, Y., Lu, W., Chen, G., Zhang, H. et al., Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound beta-phenylethyl isothiocyanate. Blood 2010, 116, 2732-2741.
179. Rausch, V., Liu, L., Kallifatidis, G., Baumann, B. et al., Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res. 2010, 70, 5004-5013.
180. Wang, X., Govind, S., Sajankila, S. P., Mi, L. et al., Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin. Mol. Nutr. Food Res. 2011, 55, 1572-1581.
181. Wang, X. F., Wu, D. M., Li, B. X., Lu, Y. J. et al., Synergistic inhibitory effect of sulforaphane and 5-fluorouracil in high and low metastasis cell lines of salivary gland adenoid cystic carcinoma. Phytother. Res. 2009, 23, 303-307.
182. el-Bayoumy, K., Upadhyaya, P., Desai, D. H., Amin, S. et al., Effects of 1, 4-phenylenebis(methylene)selenocyanate, phenethyl isothiocyanate, indole-3-carbinol, and d-limonene individually and in combination on the tumorigenicity of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung. Anticancer Res. 1996, 16, 2709-2712.
183. Kotowski, U., Heiduschka, G., Brunner, M., Czembirek, C. et al., Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane. Strahlentherapie und Onkologie 2011, 187, 575-580.
184. Doudican, N. A., Wen, S. Y., Mazumder, A., Orlow, S. J., Sulforaphane synergistically enhances the cytotoxicity of arsenic trioxide in multiple myeloma cells via stress-mediated pathways. Oncol. Rep. 2012, 28, 1851-1858.
185. Jiang, H., Shang, X., Wu, H., Huang, G. et al., Combination treatment with resveratrol and sulforaphane induces apoptosis in human U251 glioma cells. Neurochem. Res. 2010, 35, 152-161.
186. Srivastava, R. K., Tang, S. N., Zhu, W., Meeker, D. et al., Sulforaphane synergizes with quercetin to inhibit self-renewal capacity of pancreatic cancer stem cells. Front. Biosci. 2011, 3, 515-528.
187. Pradhan, S. J., Mishra, R., Sharma, P., Kundu, G. C., Quercetin and sulforaphane in combination suppress the progression of melanoma through the down-regulation of matrix metalloproteinase-9. Exp. Ther. Med. 2010, 1, 915-920.
188. Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A. et al., Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 1997, 277, 818-821.
189. Koschny, R., Walczak, H., Ganten, T. M., The promise of TRAIL-potential and risks of a novel anticancer therapy. J. Mol. Med. 2007, 85, 923-935.
190. Shankar, S., Srivastava, R. K., Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist. Updat. 2004, 7, 139-156.
191. Wicker, C. A., Sahu, R. P., Kulkarni-Datar, K., Srivastava, S. K. et al., BITC sensitizes pancreatic adenocarcinomas to TRAIL-induced apoptosis. Cancer Growth Metastasis 2010, 2009, 45-55.
192. Di Pasqua, A. J., Hong, C., Wu, M. Y., McCracken, E. et al., Sensitization of non-small cell lung cancer cells to cisplatin by naturally occurring isothiocyanates. Chem. Res. Toxicol. 2010, 23, 1307-1309.
193. Fimognari, C., Lenzi, M., Sciuscio, D., Cantelli-Forti, G. et al., Combination of doxorubicin and sulforaphane for reversing doxorubicin-resistant phenotype in mouse fibroblasts with p53Ser220 mutation. Ann. N. Y. Acad. Sci. 2007, 1095, 62-69.
194. Mukherjee, S., Dey, S., Bhattacharya, R. K., Roy, M., Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells. Mol. Cell. Biochem. 2009, 330, 9-22.
195. Liu, K., Cang, S., Ma, Y., Chiao, J. W., Synergistic effect of paclitaxel and epigenetic agent phenethyl isothiocyanate on growth inhibition, cell cycle arrest and apoptosis in breast cancer cells. Cancer Cell Int. 2013, 13, 10.
196. Kaminski, B. M., Weigert, A., Brune, B., Schumacher, M. et al., Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death. Cancer Chemother. Pharmacol. 2011, 67, 1167-1178.
197. Kallifatidis, G., Rausch, V., Baumann, B., Apel, A. et al., Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling. Gut 2009, 58, 949-963.
198. Milczarek, M., Misiewicz-Krzeminska, I., Lubelska, K., Wiktorska, K., Combination treatment with 5-fluorouracil and isothiocyanates shows an antagonistic effect in Chinese hamster fibroblast cells line-V79. Acta Pol. Pharm. 2011, 68, 331-342.
199. Kandala, P. K., Srivastava, S. K., DIMming ovarian cancer growth. Curr. Drug Targets 2012, 13, 1869-1875.
200. Pappa, G., Strathmann, J., Lowinger, M., Bartsch, H. et al., Quantitative combination effects between sulforaphane and 3, 3'-diindolylmethane on proliferation of human colon cancer cells in vitro. Carcinogenesis 2007, 28, 1471-1477.
201. Hutzen, B., Willis, W., Jones, S., Cen, L. et al., Dietary agent, benzyl isothiocyanate inhibits signal transducer and activator of transcription 3 phosphorylation and collaborates with sulforaphane in the growth suppression of PANC-1 cancer cells. Cancer Cell Int. 2009, 9, 24.
202. Hecht, S. S., Kenney, P. M., Wang, M., Trushin, N. et al., 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. 2000, 150, 49-56.
203. Shishodia, S., Chaturvedi, M. M., Aggarwal, B. B., Role of curcumin in cancer therapy. Curr. Probl. Cancer 2007, 31, 243-305.
204. Sahu, R. P., Batra, S., Srivastava, S. K., Activation of ATM/Chk1 by curcumin causes cell cycle arrest and apoptosis in human pancreatic cancer cells. Br. J. Cancer 2009, 100, 1425-1433.
205. Cheung, K. L., Khor, T. O., Kong, A. N., Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation. Pharm. Res. 2009, 26, 224-231.
206. Thakkar, A., Sutaria, D., Grandhi, B. K., Wang, J. et al., The molecular mechanism of action of aspirin, curcumin and sulforaphane combinations in the chemoprevention of pancreatic cancer. Oncol. Rep. 2013, 29, 1671-1677.
207. Barve, A., Khor, T. O., Hao, X., Keum, Y. S. et al., Murine prostate cancer inhibition by dietary phytochemicals-curcumin and phenyethylisothiocyanate. Pharm. Res. 2008, 25, 2181-2189.
208. Khor, T. O., Keum, Y. S., Lin, W., Kim, J. H. et al., Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Res. 2006, 66, 613-621.
209. Kim, J. H., Xu, C., Keum, Y. S., Reddy, B. et al., Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis 2006, 27, 475-482.
210. Singh, B. N., Shankar, S., Srivastava, R. K., Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem. Pharmacol. 2011, 82, 1807-1821.
211. Nair, S., Barve, A., Khor, T. O., Shen, G. X. et al., Regulation of Nrf2- and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells. Acta Pharmacol. Sin. 2010, 31, 1223-1240.
212. Chen, H., Landen, C. N., Li, Y., Alvarez, R. D. et al., Epigallocatechin gallate and sulforaphane combination treatment induce apoptosis in paclitaxel-resistant ovarian cancer cells through hTERT and Bcl-2 down-regulation. Exp. Cell Res. 2013, 319, 697-706.
213. De Nicola, G. R., Montaut, S., Rollin, P., Nyegue, M., Stability of benzylic-type isothiocyanates in hydrodistillation-mimicking conditions. J. Agric. Food Chem. 2013, 61, 137-142.
214. Franklin, S. J., Dickinson, S. E., Karlage, K. L., Bowden, G. T. et al., Stability of sulforaphane for topical formulation. Drug Dev. Ind. Pharm. 2013.