Exploring the effects of isothiocyanates on chemotherapeutic drugs

Expert Opinion on Drug Metabolism and Toxicology

Volumn 10, Issue 1, 2014, Pages 25-38

  Minarini, Anna ^a   Milelli, Andrea ^a   Fimognari, Carmela ^a   Simoni, Elena ^a   Turrini, Eleonora ^a   Tumiatti, Vincenzo ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Chemoprevention; Chemotherapeutic drugs; Combination therapy; Isothiocyanate; Pharmacokinetic interactions

Indexed keywords

1 NAPHTHYL ISOTHIOCYANATE; ALLYL ISOTHIOCYANATE; ANTINEOPLASTIC AGENT; BENZYL ISOTHIOCYANATE; BREAST CANCER RESISTANCE PROTEIN; CISPLATIN; DAUNORUBICIN; DOCETAXEL; DOXORUBICIN; ERYSOLIN; ETOPOSIDE; FLUDARABINE; FLUOROURACIL; GEMCITABINE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; ISOTHIOCYANIC ACID DERIVATIVE; METFORMIN; MITOMYCIN; MITOXANTRONE; MULTIDRUG RESISTANCE PROTEIN 1; OXALIPLATIN; PACLITAXEL; PHENETHYL ISOTHIOCYANATE; PROTEIN BAX; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); SORAFENIB; SULFORAPHANE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINBLASTINE; VORINOSTAT;

ADENOID CYSTIC CARCINOMA; ADVANCED CANCER; ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT RESPONSIVE ELEMENT; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; AREA UNDER THE CURVE; BREAST CANCER; BROCCOLI; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER STEM CELL; CELL CYCLE ARREST; CELL DEATH; CELL VIABILITY; CHEMOPROPHYLAXIS; CHRONIC LYMPHATIC LEUKEMIA; DOWN REGULATION; DRUG ABSORPTION; DRUG ACCUMULATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; DRUG TRANSFORMATION; ELECTROPHILICITY; ENZYME ACTIVITY; HEMATOLOGIC DISEASE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTRACELLULAR SIGNALING; LEUKEMIA; LIPOPHILICITY; MAXIMUM PLASMA CONCENTRATION; METABOLITE; NON INSULIN DEPENDENT DIABETES MELLITUS; NUCLEOPHILICITY; OXIDATIVE STRESS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; PROTEIN EXPRESSION; REVIEW; SALIVARY GLAND TUMOR; SOLID TUMOR; UPREGULATION;

ANIMALS; ANTICARCINOGENIC AGENTS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CHEMOPREVENTION; DIET; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; FOOD-DRUG INTERACTIONS; HUMANS; ISOTHIOCYANATES; NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84890319279     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1517/17425255.2013.843668     Document Type: Review

References (108)

1. WHO. Cancer Fact Sheet N-297. Available from: Http://www.who.int/ mediacentre/factsheets/fs297/en/ [Last accessed 28 July 2013
2. Sporn MB, Suh N. Chemoprevention of cancer. Carcinogenesis 2000;21:525-30
3. Higdon JV, Delage B, Williams DE, Dashwood RH. Cruciferous vegetables and human cancer risk: Epidemiologic evidence and mechanistic basis. Pharmacol Res 2007;55:224-36
4. Sonderby IE, Geu-Flores F, Halkier BA. Biosynthesis of glucosinolates-gene discovery and beyond. Trends Plant Sci 2010;15:283-90
5. Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 2001;56:5-51
6. Fahey JW, Wehage SL, Holtzclaw WD, et al. Protection of humans by plant glucosinolates: Efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora. Cancer Prev Res (Phila) 2012;5:603-11
7. Lamy E, Scholtes C, Herz C, Mersch-Sundermann V. Pharmacokinetics and pharmacodynamics of isothiocyanates. Drug Metab Rev 2011;43:387-407
8. Clarke JD, Dashwood RH, Ho E. Multi-Targeted prevention of cancer by sulforaphane. Cancer Lett 2008;269:291-304
9. Sarkar FH, Li YW. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy. Acta Pharmacol Sin 2007;28:1305-15
10. Shapiro TA, Fahey JW, Dinkova-Kostova AT, et al. Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: A clinical phase I study. Nutr Cancer 2006;55:53-62
11. Ji Y, Morris ME. Determination of phenethyl isothiocyanate in human plasma and urine by ammonia derivatization and liquid chromatography-Tandem mass spectrometry. Anal Biochem 2003;323:39-47
12. Gasper AV, Al-Janobi A, Smith JA, et al. Glutathione S-Transferase M1 polymorphism and metabolism of sulforaphane from standard and high-glucosinolate broccoli. Am J Clin Nutr 2005;82:1283-91
13. Zhang Y. Molecular mechanism of rapid cellular accumulation of anticarcinogenic isothiocyanates. Carcinogenesis 2001;22:425-31
14. Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J 2002;364:301-7
15. Kerr I, Simpkins NS. ABC transporters and ITC. Lett Drug Des Discov 2006;3:607-21
16. Hecht SS. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev 2000;32:395-411
17. Kensler TW, Ng D, Carmella SG, et al. Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Carcinogenesis 2012;33:101-7
18. Tseng E, Scott-Ramsay EA, Morris ME. Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines. Exp Biol Med (Maywood) 2004;229:835-42
19. Hsu YC, Chang SJ, Wang MY, et al. Growth inhibition and apoptosis of neuroblastoma cells through ROS-independent MEK/ERK activation by sulforaphane. Cell Biochem Biophys 2013
20. Xu K, Thornalley PJ. Studies on the mechanism of the inhibition of human leukaemia cell growth by dietary isothiocyanates and their cysteine adducts in vitro. Biochem Pharmacol 2000;60:221-31
21. Xu C, Shen G, Yuan X, 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;27:437-45
22. Mi L, Wang X, Govind S, et al. The role of protein binding in induction of apoptosis by phenethyl isothiocyanate and sulforaphane in human non-small lung cancer cells. Cancer Res 2007;67:6409-16
23. Chen MJ, Tang WY, Hsu CW, et al. Apoptosis induction in primary human colorectal cancer cell lines and retarded tumor growth in SCID mice by sulforaphane. Evid Based Complement Alternat Med 2012;2012:415231
24. Wu X, Zhou QH, Xu K. Are isothiocyanates potential anti-cancer drugs? Acta Pharmacol Sin 2009;30:501-12
25. Conaway CC, Yang YM, Chung FL. Isothiocyanates as cancer chemopreventive agents: Their biological activities and metabolism in rodents and humans. Curr Drug Metab 2002;3:233-55
26. Hayes JD, McMahon M. NRF2 and KEAP1 mutations: Permanent activation of an adaptive response in cancer. Trends Biochem Sci 2009;34:176-88
27. Payen L, Courtois A, Loewert M, et al. Reactive oxygen species-related induction of multidrug resistance-Associated protein 2 expression in primary hepatocytes exposed to sulforaphane. Biochem Biophys Res Commun 2001;282:257-63
28. Kalra S, Zhang Y, Knatko EV, et al. Oral azathioprine leads to higher incorporation of 6-Thioguanine in DNA of skin than liver: The protective role of the Keap1/Nrf2/ARE pathway. Cancer Prevent Res 2011;4:1665-74
29. Dietrich CG, Ottenhoff R, de Waart DR, Oude Elferink RP. Role of MRP2 and GSH in intrahepatic cycling of toxins. Toxicology 2001;167:73-81
30. Gamet-Payrastre L. Signaling pathways and intracellular targets of sulforaphane mediating cell cycle arrest and apoptosis. Curr Cancer Drug Targets 2006;6:135-45
31. Hwang ES, Lee HJ. Effects of phenylethyl isothiocyanate and its metabolite on cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells. Int J Food Sci Nutr 2010;61:324-36
32. Herman-Antosiewicz A, Xiao H, Lew KL, Singh SV. Induction of p21 protein protects against sulforaphane-induced mitotic arrest in LNCaP human prostate cancer cell line. Mol Cancer Ther 2007;6:1673-81
33. Shen G, Xu C, Chen C, 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;57:317-27
34. Singh SV, Srivastava SK, Choi S, et al. Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem 2005;280:19911-24
35. Mi L, Di Pasqua AJ, Chung FL. Proteins as binding targets of isothiocyanates in cancer prevention. Carcinogenesis 2011;32:1405-13
36. Cavell BE, Syed Alwi SS, Donlevy A, Packham G. Anti-Angiogenic effects of dietary isothiocyanates: Mechanisms of action and implications for human health. Biochem Pharmacol 2011;81:327-36
37. Myzak MC, Karplus PA, Chung FL, Dashwood RH. A novel mechanism of chemoprotection by sulforaphane: Inhibition of histone deacetylase. Cancer Res 2004;64:5767-74
38. Singh SV, Singh K. Cancer chemoprevention with dietary isothiocyanates mature for clinical translational research. Carcinogenesis 2012;33:1833-42
39. Navarro SL, Li F, Lampe JW. Mechanisms of action of isothiocyanates in cancer chemoprevention: An update. Food Funct 2011;2:579-87
40. Zhang YS. The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates. Carcinogenesis 2012;33:2-9
41. Dinkova-Kostova AT, Kostov RV. Glucosinolates and isothiocyanates in health and disease. Trends Mol Med 2012;18:337-47
42. Powolny A, Bommareddy A, Singh S. Slow but steady progress in cancer chemoprevention with phenethyl isothiocyanate: Fulfilled promises and translational challenges. In: Sarkar FH, editor. Nutraceuticals and cancer. Springer Science+Business Media; Germany: 2012. p. 231-58
43. Zhang Y. Allyl isothiocyanate as a cancer chemopreventive phytochemical. Mol Nutr Food Res 2010;54:127-35
44. Clarke JD, Hsu A, Yu Z, et al. Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells. Mol Nutr Food Res 2011;55:999-1009
45. Wang X, Doherty GP, Leith MK, et al. Enhanced cytotoxicity of mitomycin C in human tumour cells with inducers of DT-diaphorase. Br J Cancer 1999;80:1223-30
46. Rockwell S, Sartorelli AC, Tomasz M, Kennedy KA. Cellular pharmacology of quinone bioreductive alkylating agents. Cancer Metastasis Rev 1993;12:165-76
47. Digby T, Leith MK, Thliveris JA, Begleiter A. Effect of NQ01 induction on the antitumor activity of RH1 in human tumors in vitro and in vivo. Cancer Chemother Pharmacol 2005;56:307-16
48. Tseng E, Kamath A, Morris ME. Effect of organic isothiocyanates on the P-glycoprotein-And MRP1-mediated transport of daunomycin and vinblastine. Pharm Res 2002;19:1509-15
49. Ji Y, Morris ME. Effect of organic isothiocyanates on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 2004;21:2261-9
50. Liebes L, Conaway CC, Hochster H, et al. High-performance liquid chromatography-based determination of total isothiocyanate levels in human plasma: Application to studies with 2-phenethyl isothiocyanate. Anal Biochem 2001;291:279-89
51. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 1999;57:727-41
52. Thorn CF, Oshiro C, Marsh S, et al. Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharmacogenet Genomics 2011;21:440-6
53. Zanichelli F, Capasso S, Di Bernardo G, et al. Low concentrations of isothiocyanates protect mesenchymal stem cells from oxidative injuries, while high concentrations exacerbate DNA damage. Apoptosis 2012;17:964-74
54. Fimognari C, Lenzi M, Sestili P, et al. Sulforaphane potentiates RNA damage induced by different xenobiotics. PLoS One 2012;7:e35267
55. Ravi D, Das KC. Redox-cycling of anthracyclines by thioredoxin system: Increased superoxide generation and DNA damage. Cancer Chemother Pharmacol 2004;54:449-58
56. Fimognari C, Nusse M, Lenzi M, et al. Sulforaphane increases the efficacy of doxorubicin in mouse fibroblasts characterized by p53 mutations. Mutat Res 2006;601:92-101
57. Fimognari C, Lenzi M, Sciuscio D, et al. Combination of doxorubicin and sulforaphane for reversing doxorubicin-resistant phenotype in mouse fibroblasts with p53Ser220 mutation. Ann NY Acad Sci 2007;1095:62-9
58. Geisler S, Lonning PE, Aas T, et al. Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res 2001;61:2505-12
59. Mukherjee S, Dey S, Bhattacharya RK, 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
60. Shay JW, Wright WE. Telomerase therapeutics for cancer: Challenges and new directions. Nat Rev Drug Discov 2006;5:577-84
61. Kim YW, Hur SY, Kim TE, et al. Protein kinase C modulates telomerase activity in human cervical cancer cells. Exp Mol Med 2001;33:156-63
62. Chang JT, Lu YC, Chen YJ, et al. hTERT phosphorylation by PKC is essential for telomerase holoprotein integrity and enzyme activity in head neck cancer cells. Br J Cancer 2006;94:870-8
63. Mukherjee S, Bhattacharya RK, Roy M. 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 2009;28:269-82
64. Jakubikova J, Cervi D, Ooi M, et al. Anti-Tumor activity and signaling events triggered by the isothiocyanates, sulforaphane and phenethyl isothiocyanate, in multiple myeloma. Haematologica 2011;96:1170-9
65. Baldwin EL, Osheroff N. Etoposide, topoisomerase II and cancer. Curr Med Chem Anticancer Agents 2005;5:363-72
66. Trachootham D, Zhang H, Zhang W, et al. Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism. Blood 2008;112:1912-22
67. Garcia-Manero G, Yang H, Bueso-Ramos C, et al. Phase 1 study of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid [SAHA]) in patients with advanced leukemias and myelodysplastic syndromes. Blood 2008;111:1060-6
68. Hu Y, Lu W, Chen G, et al. Overcoming resistance to histone deacetylase inhibitors in human leukemia with the redox modulating compound beta-phenylethyl isothiocyanate. Blood 2010;116:2732-41
69. Ibrahim N, Yu Y, Walsh WR, Yang JL. Molecular targeted therapies for cancer: Sorafenib mono-Therapy and its combination with other therapies (review). Oncol Rep 2012;27:1303-11
70. Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-Term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 2009;15:232-9
71. Kallifatidis G, Rausch V, Baumann B, et al. Sulforaphane targets pancreatic tumour-initiating cells by NF-kappaB-induced antiapoptotic signalling. Gut 2009;58:949-63
72. Rausch V, Liu L, Kallifatidis G, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res 2010;70:5004-13
73. Zhang J, Peng B. In vitro angiogenesis and expression of nuclear factor kappaB and VEGF in high and low metastasis cell lines of salivary gland Adenoid Cystic Carcinoma. BMC Cancer 2007;7:95
74. Wang XF, Wu DM, Li BX, 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;23:303-7
75. 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;68:331-42
76. Mutch DG, Bloss JD. Gemcitabine in cervical cancer. Gynecol Oncol 2003;90:S8-15
77. Park SY, Kim GY, Bae SJ, et al. Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3. Oncol Rep 2007;18:181-7
78. Sharma C, Sadrieh L, Priyani A, et al. Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells. Cancer Epidemiol 2011;35:272-8
79. Pantschenko AG, Pushkar I, Anderson KH, et al. The interleukin-1 family of cytokines and receptors in human breast cancer: Implications for tumor progression. Int J Oncol 2003;23:269-84
80. Kallifatidis G, Labsch S, Rausch V, et al. Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol Ther 2011;19:188-95
81. Dontu G, Jackson KW, McNicholas E, et al. Role of Notch signaling in cell-fate determination of human mammary stem/ progenitor cells. Breast Cancer Res 2004;6:R605-15
82. Moreb JS. Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther 2008;3:237-46
83. Raymond E, Faivre S, Chaney S, et al. Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther 2002;1:227-35
84. Kaminski BM, Weigert A, Brune B, 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;67:1167-78
85. Tang HL, Yuen KL, Tang HM, Fung MC. Reversibility of apoptosis in cancer cells. Br J Cancer 2009;100:118-22
86. Siddik ZH. Cisplatin: Mode of cytotoxic action and molecular basis of resistance. Oncogene 2003;22:7265-79
87. Wang X, Govind S, Sajankila SP, et al. Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin. Mol Nutr Food Res 2011;55:1572-81
88. Lee Y, Kim YJ, Choi YJ, et al. Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in HL-60 cells. Food Chem Toxicol 2012;50:2397-406
89. Di Pasqua AJ, Hong C, Wu MY, et al. Sensitization of non-small cell lung cancer cells to cisplatin by naturally occurring isothiocyanates. Chem Res Toxicol 2010;23:1307-9
90. Petrylak DP. New paradigms for advanced prostate cancer. Rev Urol 2007;9(Suppl 2):S3-S12
91. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004;4:253-65
92. Ganansia-Leymarie V, Bischoff P, Bergerat JP, Holl V. Signal transduction pathways of taxanes-induced apoptosis. Curr Med Chem Anticancer Agents 2003;3:291-306
93. Hardy TM, Tollefsbol TO. Epigenetic diet: Impact on the epigenome and cancer. Epigenomics 2011;3:503-18
94. Xiao D, Singh SV. Phenethyl isothiocyanate-induced apoptosis in p53-deficient PC-3 human prostate cancer cell line is mediated by extracellular signal-regulated kinases. Cancer Res 2002;62:3615-19
95. Liu K, Cang S, Ma Y, Chiao JW. 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
96. Xiao D, Singh SV. Phenethyl isothiocyanate sensitizes androgen-independent human prostate cancer cells to docetaxel-induced apoptosis in vitro and in vivo. Pharm Res 2010;27:722-31
97. Rattan R, Giri S, Hartmann LC, Shridhar V. Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner. J Cell Mol Med 2011;15:166-78
98. Xiao D, Powolny AA, Moura MB, et al. Phenethyl isothiocyanate inhibits oxidative phosphorylation to trigger reactive oxygen species-mediated death of human prostate cancer cells. J Biol Chem 2010;285:26558-69
99. Chan DK, Miskimins WK. Metformin and phenethyl isothiocyanate combined treatment in vitro is cytotoxic to ovarian cancer cultures. J Ovarian Res 2012;5:19
100. Minarini A, Milelli A, Tumiatti V, et al. Design, synthesis and biological evaluation of new naphtalene diimides bearing isothiocyanate functionality. Eur J Med Chem 2012;48:124-31
101. Kim JH, Xu C, Keum YS, et al. Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with beta-phenylethyl isothiocyanate and curcumin. Carcinogenesis 2006;27:475-82
102. Peto J. Cancer epidemiology in the last century and the next decade. Nature 2001;411:390-5
103. Hecht SS, Chung FL, Richie JP Jr, et al. Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers. Cancer Epidemiol Biomarkers Prev 1995;4:877-84
104. Wang X, Di Pasqua AJ, Govind S, et al. Selective depletion of mutant p53 by cancer chemopreventive isothiocyanates and their structure-Activity relationships. J Med Chem 2011;54:809-16. From this study performed on different ITCs, PEITC emerges as the most potent agent in depleting mutant p53
105. World Cancer Research Fund/American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: A global perspective. AICR; Washington DC: 2007
106. Ogawa K, Hirose M, Sugiura S, et al. Dose-dependent promotion by phenylethyl isothiocyanate, a known chemopreventer, of two-stage rat urinary bladder and liver carcinogenesis. Nutr Cancer 2001;40:134-9
107. Jiang T, Chen N, Zhao F, et al. High levels of Nrf2 determine chemoresistance in type II endometrial cancer. Cancer Res 2010;70:5486-96
108. Slocum SL, Kensler TW. Nrf2: Control of sensitivity to carcinogens. Arch Toxicol 2011;85:273-84