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01.06.2015 | Review

Isothiocyanates: a class of bioactive metabolites with chemopreventive potential

verfasst von: Gaurav Kumar, Hardeep Singh Tuli, Sonam Mittal, Jitendra Kumar Shandilya, Anil Tiwari, Sardul Singh Sandhu

Erschienen in: Tumor Biology | Ausgabe 6/2015

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Abstract

In recent years, growing interest has been focused on the field of chemoprevention using natural therapies. The reason to turn toward “natural” remedies is associated with diverse beneficial pharmacological properties of natural compounds. Isothiocyanates (ITCs), the major pharmacological active constituents of cruciferous vegetables, are derived from the enzymatic hydrolysis of glucosinolates (GSLs). ITCs govern many intracellular targets including cytochrome P 450 (CYP) enzymes, proteins involved in antioxidant response, tumorigenesis, apoptosis, cell cycle, and metastasis. Investigation of the mechanisms of anti-cancer drugs has given important information regarding the use of natural chemopreventive compounds. This extensive review covers various molecular aspects of the interactions of ITCs with their recognized cellular targets involved in cancer treatment in order to enhance anti-tumor outcome with decreased toxicity to patients.

Xiang WU, Zhou QH, Ke XU. Are isothiocyanates potential anti-cancer drugs? Acta Pharmacol Sin. 2009;30:501–12.

Melchini A, Traka MH. Biological profile of erucin: a new promising anticancer agent from cruciferous vegetables. Toxins (Basel). 2010;2:593–12.

Lambrix V, Reichelt M, Mitchell-Olds T, Kliebenstein DJ, Gershenzon J. The Arabidopsis epithiospecifier protein promotes the hydrolysis of glucosinolates to nitriles and influences Trichoplusia ni Herbivory. Plant Cell. 2001;13:2793–807.PubMedPubMedCentral

Halkier BA, Gershenzon J. Biology and biochemistry of glucosinolates. Annu Rev Plant Biol. 2006;57:303–33.PubMed

Gimsing AL, Kirkegaard JA. Glucosinolates and biofumigation: fate of glucosinolates and their hydrolysis products in soil. Phytochem Rev. 2009;8:299–10.

Rose P, Huang Q, Ong CN, Whiteman M. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells. Toxicol Appl Pharm. 2005;209:105–13.

Brown KK, Blaikie FH, Smith RA, Tyndall JD, Lue H, Bernhagen J, et al. Direct modification of the proinflammatory cytokine macrophage migration inhibitory factor by dietary isothiocyanates. J Biol Chem. 2009;284:32425–33.PubMedPubMedCentral

Yuesheng Z. The molecular basis that unifies the metabolism cellular uptake and chemopreventive activities of dietary isothiocyanates. Carcinogenesis. 2012;33:2–9.

Brown KK, Hampton MB. Biological targets of isothiocyanates. Biochim Biophys Acta. 1810;2011:888–94.

10.

Lai KC, Huang AC, Hsu SC, Kuo CL, Yang JS, Wu SH, et al. Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway. J Agric Food Chem. 2010;58:2935–42.PubMed

11.

Hecht SS. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev. 2000;32:395–411.PubMed

12.

Smith TJ. Mechanisms of carcinogenesis inhibition by isothiocyanates. Expert Opin Investig Drugs. 2001;10:2167–74.PubMed

13.

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.PubMed

14.

Guo Z, Smith TJ, Wang E, Sadrieh N, Ma Q, Thomas PE, et al. Effects of phenethyl isothiocyanate a carcinogenesis inhibitor on xenobiotic-metabolizing enzymes and nitrosamine metabolism in rats. Carcinogenesis. 1992;13:2205–10.PubMed

15.

Smith TJ, Guo Z, Guengerich FP, Yang CS. Metabolism of 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) by human cytochrome P450 1A2 and its inhibition by phenethyl isothiocyanate. Carcinogenesis. 1996;17:809–13.PubMed

16.

Nakajima M, Yoshida R, Shimada N, Yamazaki H, Yokoi T. Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Drug Metab Dispos. 2001;29:1110–3.PubMed

17.

Goosen TC, Kent UM, Brand L, Hollenberg PF. Inactivation of cytochrome P450 2B1 by benzyl isothiocyanate a chemopreventive agent from cruciferous vegetables. Chem Res Toxicol. 2000;13:1349–59.PubMed

18.

Hanlon N, Okpara A, Coldham N, Sauer MJ, Ioannides C. Modulation of rat hepatic and pulmonary cytochromes P450 and phase II enzyme systems by erucin, an isothiocyanate structurally related to sulforaphane. J Agric Food Chem. 2008;56:7866–71.PubMed

19.

Cheung KL, Kong AN. Molecular targets of dietary phenethyl isothiocyanate and Sulforaphane for cancer chemoprevention. AAPS J. 2010;12:87–97.PubMed

20.

La Marca M, Beffy P, Della Croce C, Gervasi PG, Iori R, Puccinelli E, et al. Structural influence of isothiocyanates on expression of cytochrome P450, phase II enzymes, and activation of Nrf2 in primary rat hepatocytes. Food Chem Toxicol. 2012;50:2822–30.PubMed

21.

Kwak MK, Egner PA, Dolan PM, Ramos-Gomez M, Groopman JD, Itoh K, et al. Role of phase 2 enzyme induction in chemoprotection by dithiolethiones. Mutat Res. 2001;480–481:305–15.PubMed

22.

Tan XL, Spivack SD. Dietary chemoprevention strategies for induction of phase II xenobiotic-metabolizing enzymes in lung carcinogenesis: a review. Lung Cancer. 2009;65:129–37.PubMedPubMedCentral

23.

Kansanen E, Kivela AM, Levonen AL. Regulation of Nrf2-dependent gene expression by 15-deoxy-Delta12,14-prostaglandin J2. Free Radic Biol Med. 2009;47:1310–7.PubMed

24.

Taguchi K, Motohashi H, Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells. 2011;16:123–40.PubMed

25.

Kansanen E, Jyrkkanen HK, Levonen AL. Activation of stress signaling pathways by electrophilic oxidized and nitrated lipids. Free Radic Biol Med. 2012;52:973–82.PubMed

26.

Dinkova-Kostova AT, Holtzclaw WD, Cole RN, Itoh K, Wakabayashi N, Katoh Y, et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci. 2002;99:11908–13.PubMedPubMedCentral

27.

Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9:668–78.PubMed

28.

Fahey JW, Haristoy X, Dolan PM, Kensler TW, Scholtus I, Stephenson KK, et al. Sulforaphane inhibits extracellular intracellular and antibiotic-resistant strains of Helicobacter pylori and prevents benzo (a) pyrene-induced stomach tumors. Proc Natl Acad Sci. 2002;99:7610–5.PubMedPubMedCentral

29.

Xu C, Huang MT, Shen G, Yuan X, Lin W, Khor TO, et al. Inhibition of 712-dimethylbenz (a) anthracene-induced skin tumorigenesis in C57BL/6 mice by sulforaphane is mediated by nuclear factor E2-related factor 2. Cancer Res. 2006;66:8293–6.PubMed

30.

Zhang Y, Talalay P. Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic phase 2 enzymes. Cancer Res. 1998;58:4632–9.PubMed

31.

Abdull Razis AF, Bagatta M, De Nicola GR, Iori R, Ioannides C. Induction of epoxide hydrolase and glucuronosyl transferase by isothiocyanates and intact glucosinolates in precision-cut rat liver slices: importance of side chain substituent and chirality. Arch oxicol. 2011;85:919–27.

32.

Kassahun K, Davis M, Hu P, Martin B, Baillie T. Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates. Chem Res Toxicol. 1997;10:1228–33.PubMed

33.

Clarke JD, Hsu A, Riedl K, Bella D, Schwartz SJ, Stevens JF, et al. Bioavailability and inter-conversion of sulforaphane and erucin in human subjects consuming broccoli sprouts or broccoli supplement in a cross-over study design. Pharmacol Res. 2011;64:456–63.PubMedPubMedCentral

34.

Yu R, Chen C, Mo YY, Hebbar V, Owuor ED, Tan TH, et al. Activation of mitogen-activated protein kinase pathways induces antioxidant response element-mediated gene expression via a Nrf2-dependent mechanism. J Biol Chem. 2000;275:39907–13.PubMed

35.

Yu R, Lei W, Mandlekar S, Weber MJ, Der CJ, Wu J, et al. Role of a mitogen activated protein kinase pathway in the induction of phase II detoxifying enzymes by hemicals. J Biol Chem. 1999;274:27545–52.PubMed

36.

Hu R, Hebbar V, Kim BR, Chen C, Winnik B, Buckley B, et al. In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat. J Pharmacol Exp Ther. 2004;310:263–71.PubMed

37.

Tuli HS, Sandhu SS, Sharma AK, Kashyap D. Cordycepin: a bioactive metabolite with therapeutic potential. Life Sci. 2013;93:863–9.PubMed

38.

Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase 9 complex initiates an poptotic protease cascade. Cell. 1997;91:479–89.PubMed

39.

Yu R, Mandlekar S, Harvey KJ, Ucker DS, Kong AN. Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity. Cancer Res. 1998;58:402–8.PubMed

40.

Singh AV, Xiao D, Lew KL, Dhir R, Singh SV. Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis. 2004;25:83–90.PubMed

41.

Basu A, Haldar S. Dietary isothiocyanate mediated apoptosis of human cancer cells is associated with Bcl-xL phosphorylation. Int J Oncol. 2008;33:657–63.PubMed

42.

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;62:3615–9.PubMed

43.

Hu R, Kim BR, Chen C, Hebbar V, Kong AN. The roles of JNK and apoptotic signaling pathways in PEITC mediated responses in human HT-29 colon adenocarcinoma cells. Carcinogenesis. 2003;24:1361–7.PubMed

44.

Lui VWY, Wentzel AL, Xiao D, Lew KL, Singh SV, Grandis JR. Requirement of a carbon spacer in benzyl isothiocyanate-mediated cytotoxicity and MAPK activation in head and neck squamous cell carcinoma. Carcinogenesis. 2003;24:1705–12.PubMed

45.

Xu K, Thornalley PJ. Signal transduction activated by the cancer chemopreventive isothiocyanates: cleavage of BID protein tyrosinase phosphorylation and activation of JNK. Brit J Cancer. 2001;84:670–3.PubMedPubMedCentral

46.

Xiao D, Srivastava SK, Lew KL, Zeng Y, Hershberger P, Johnson CS, et al. Allyl isothiocyanate a constituent of cruciferous vegetables inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis. Carcinogenesis. 2003;24:891–7.PubMed

47.

Chen YR, Wang W, Kong AN, Tan TH. Molecular mechanisms of c-Jun N-terminal kinase-mediated apoptosis induced by anticarcinogenic isothiocyanates. J Biol Chem. 1998;273:1769–75.PubMed

48.

Fimognari C, Nusse M, Cesari R, Iori R, Cantelli-Forti G, Hrelia P. Growth inhibition cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane. Carcinogenesis. 2002;23:581–6.PubMed

49.

Srivastava SK, Xiao D, Lew KL, Hershberger P, Kokkinakis DM, Johnson CS, et al. Allyl isothiocyanate a constituent of cruciferous vegetables inhibits growth of PC-3 human prostate cancer xenografts in vivo. Carcinogenesis. 2003;24:1665–70.PubMed

50.

Devi JR, Thangam EB. Mechanisms of anticancer activity of sulforaphane from Brassica oleracea in HEp-2 human epithelial carcinoma cell line. Asian Pac J Cancer Prev. 2012;13:2095–100.PubMed

51.

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.PubMed

52.

Myzak MC, Hardin K, Wang R, Dashwood RH, Ho E. Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis. 2006;27:811–9.PubMed

53.

Beklemisheva AA, Fang Y, Feng J, Ma X, Dai W, Chiao JW. Epigenetic mechanism of growth inhibition induced by phenylhexyl isothiocyanate in prostate cancer cells. Anticancer Res. 2006;26:1225–30.PubMed

54.

Ma X, Fang Y, Beklemisheva A, Dai W, Feng J, Ahmed T, et al. Phenylhexyl isothiocyanate inhibits histone deacetylases and remodels chromatins to induce growth arrest in human leukemia cells. Int J Oncol. 2006;28:1287–93.PubMed

55.

Zhang Y, Tang L, Gonzalez V. Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol Cancer Ther. 2003;2:1045–52.PubMed

56.

Xiao D, Johnson CS, Trump DL, Singh SV. 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. 2004;3:567–75.PubMed

57.

Visanji JM, Duthie SJ, Pirie L, Thompson DG, Padfield PJ. Dietary isothiocyanates inhibit Caco-2 cell proliferation and induce G2/M phase cell cycle arrest DNA damage and G2/M checkpoint activation. J Nutr. 2004;134:3121–6.PubMed

58.

Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R, et al. Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J Biol Chem. 2004;279:25813–22.PubMed

59.

Pappa G, Bartsch H, Gerhäuser C. Biphasic modulation of cell proliferation by sulforaphane at physiologically relevant exposure times in a human colon cancer cell line. Mol Nutr Food Res. 2007;51:977–84.PubMed

60.

Cheung KL, Khor TO, Yu S, Kong AN. PEITC induces G1 cell cycle arrest on HT-29 cells through the activation of p38 MAPK signaling pathway. AAPS J. 2008;10:277–81.PubMedPubMedCentral

61.

Ho E, Dashwood RH. Dietary manipulation of histone structure and function. World Rev Nutr Diet. 2010;101:95–102.PubMedPubMedCentral

62.

Batra S, Sahu RP, Kandala PK, Srivastava SK. Benzyl isothiocyanate-mediated inhibition of histone deacetylase leads to NF-kappaB turnoff in human pancreatic carcinoma cells. Mol Cancer Ther. 2010;9:1596–608.PubMedPubMedCentral

63.

Wang LG, Liu XM, Fang Y, Dai W, Chiao FB, Puccio GM, et al. De-repression of the p21 promoter in prostate cancer cells by an isothiocyanate via inhibition of HDACs and c-Myc. Int J Oncol. 2008;33:375–80.PubMed

64.

Heiss E, Herhaus C, Klimo K, Bartsch H, Gerhauser C. Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem. 2001;276:32008–15.PubMed

65.

Xu C, Shen G, Chen C, Gelinas C, Kong AN. Suppression of NF-?B and NF-?B-regulated gene expression by sulforaphane and PEITC through I?B? IKK pathway in human prostate cancer PC-3 cells. Oncogene. 2005;24:4486–95.PubMed

66.

Ahn KS, Aggarwal BB. Transcription factor NF-kappaB: a sensor for smoke and stress signals. Ann N Y Acad Sci. 2005;1056:218–33.PubMed

67.

Lee CH, Jeon YT, Kim SH, Song YS. NF-kappaB as a potential molecular target for cancer therapy. Biofactors. 2007;29:19–35.PubMed

68.

Dutta J, Fan Y, Gupta N, Fan G, Gélinas C. Current insights into the regulation of programmed cell death by NF-kappaB. Oncogene. 2006;25:6800–16.PubMed

69.

Naugler WE, Karin M. NF-kappa B and cancer-identifying targets and mechanisms. Curr Opin Genet Dev. 2008;18:19–26.PubMedPubMedCentral

70.

Srivastava SK, Singh SV. Cell cycle arrest apoptosis induction and inhibition of nuclear factor kappa B activation in anti-proliferative activity of benzy isothiocyanate against human pancreatic cancer cells. Carcinogenesis. 2004;25:1701–9.PubMed

71.

Prawan A, Saw CL, Khor TO, Keum YS, Yu S, Hu L, et al. Anti-NF-kappaB and anti-inflammatory activities of synthetic isothiocyanates: effect of chemical structures and cellular signaling. Chem Biol Interact. 2009;179:202–11.PubMed

72.

Jeong WS, Kim IW, Hu R, Kong AN. Modulatory properties of various natural chemopreventive agents on the activation of NF kappaB signaling pathway. Pharm Res. 2004;21:661–70.PubMed

73.

Boreddy SR, Pramanik KC, Srivastava SK. Molecular targets of benzyl isothiocyanates in pancreatic cancer. In: Srivastava SK, editor. Pancreatic cancer- molecular mechanism and targets. Europe: In tech; 2012. p. 193–213.

74.

Wu X, Zhu Y, Yan H, Liu B, Li Y, Zhou Q, et al. Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells. BMC Cancer. 2010;10:269.PubMedPubMedCentral

75.

Heiss E, Gerhäuser C. Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane mediated inhibition of NF-kappaB binding to DNA. Antioxid Redox Signal. 2005;7:1601–11.PubMed

76.

Rose P, Won YK, Ong CN, Whiteman M. Beta-phenylethyl and 8-methylsulphinyloctyl isothiocyanates constituents of watercress suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 2647 macrophages. Nitric Oxide. 2005;12:237–43.PubMed

77.

Woo KJ, Kwon TK. Sulforaphane suppresses lipopolysaccharide-induced cyclooxygenase-2 (COX-2) expression through the modulation of multiple targets in COX-2 gene promoter. Int Immunopharmacol. 2007;7:1776–83.PubMed

78.

Bucala R. Identification of MIF as a new pituitary hormone and macrophage cytokine and its role in endotoxic shock. Immunol Lett. 1994;43:23–6.PubMed

79.

Bacher M, Metz CN, Calandra T, Mayer K, Chesney J, Lohoff M, et al. An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci. 1996;93:7849–54.PubMedPubMedCentral

80.

Kleemann R, Kapurniotu A, Frank RW, Gessner A, Mischke R, Flieger O, et al. Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase. J Mol Biol. 1998;280:85–102.PubMed

81.

Bell JE. MIF keeps macrophages on guard. Nat Rev Immunol. 2002;2:70.PubMed

82.

Mitchell RA, Bucala R. Tumor growth-promoting properties of macrophage migration inhibitory factor (MIF). Semin Cancer Biol. 2000;10:359–66.PubMed

83.

Bifulco C, McDaniel K, Leng L, Bucala R. Tumor growth-promoting properties of macrophage migration inhibitory factor. Curr Pharm Des. 2008;14:3790–801.PubMed

84.

Ouertatani-Sakouhi H, El-Turk F, Fauvet B, Roger T, Le Roy D, Karpinar DP, et al. A new class of isothiocyanate-based irreversible inhibitors of macrophage migration inhibitory factor (MIF). Biochemistry. 2009;48:9858–70.PubMedPubMedCentral

85.

Healy ZR, Liu H, Holtzclaw WD, Talalay P. Inactivation of tautomerase activity of macrophage migration inhibitory factor by sulforaphane: a potential biomarker for anti-inflammatory intervention. Cancer Epidemiol Biomarkers Prev. 2011;20:1516–23.PubMedPubMedCentral

86.

Crichlow GV, Fan C, Keeler C, Hodsdon M, Lolis EJ. Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer preventive isothiocyanates. Biochemistry. 2012;51:7506–14.PubMedPubMedCentral

87.

Nogales E. Structural insight into microtubule function. Annu Rev Biophys Biomol Struct. 2001;30:397–420.PubMed

88.

Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4:253–65.PubMed

89.

Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;96:643–9.

90.

White E. Life death and the pursuit of apoptosis. Genes Dev. 1996;10:1–15.PubMed

91.

Jackson SJ, Singletary KW. Sulforaphane inhibits human MCF-7 mammary cancer cell mitotic progression and tubulin polymerization. J Nutr. 2004;134:2229–36.PubMed

92.

Azarenko O, Okouneva T, Singletary KW, Jordan MA, Wilson L. Suppression of microtubule dynamic instability and turnover in MCF7 breast cancer cells by sulforaphane. Carcinogenesis. 2008;29:2360–8.PubMedPubMedCentral

93.

Mi L, Xiao Z, Hood BL, Dakshanamurthy S, Wang X, Govind S, et al. Covalent binding to tubulin by isothiocyanates A mechanism of cell growth arrest and apoptosis. J Biol Chem. 2008;283:22136–46.PubMedPubMedCentral

94.

Mi L, Gan N, Cheema A, Dakshanamurthy S, Wang X, Yang DC, et al. Cancer preventive isothiocyanates induce selective degradation of cellular alpha- and beta-tubulins by proteasomes. J Biol Chem. 2009;284:17039–51.PubMedPubMedCentral

95.

Geng F, Tang L, Li Y, Yang L, Choi KS, Kazim AL, et al. Allyl isothiocyanate arrests cancer cells in mitosis and mitotic arrest in turn leads to apoptosis via Bcl-2 phosphorylation. J Biol Chem. 2011;286:32259–67.PubMedPubMedCentral

96.

Tuli HS, Sadhu SS, Sharma AK, Kashyap D. Anti-angiogenic activity of the extracted fermentation broth of an entomopathogenic fungus, Cordyceps militaris 3936. Int J Pharm Pharm Sci. 2014;6:581–3.

97.

Battegay EJ. Angiogensis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med. 1995;73:333–46.PubMed

98.

Klagsbrun M, Moses MA. Molecular angiogenesis. Chem Biol. 1999;6:217–24.

99.

Boreddy SR, Sahu RP, Srivastava SK. Benzyl isothiocyanate suppresses pancreatic tumor angiogenesis and invasion by inhibiting HIF-a/VEGF/Rho-GTPases: pivotal role of STAT-3. PLoS One. 2011;6:e25799.PubMedPubMedCentral

100.

Xiao D, Singh SV. Phenethyl isothiocyanate inhibits angiogenesis in vitro and ex vivo. Cancer Res. 2007;67:2239–46.PubMed

101.

Gupta B, Chiang L, Chae KM, Lee DH. Phenethyl isothiocyanate inhibits hypoxia-induced accumulation of HIF-1aand VEGF expression in human glioma cells. Food Chem. 2013;141:1841–6.PubMed

102.

Gupta P, Adkins C, Lockman P, Srivastava SK. Metastasis of breast tumor cells to brain is suppressed by phenethyl isothiocyanate in a novel in vivo metastasis model. PLoS One. 2013;8:e67278.PubMedPubMedCentral

103.

Davis R, Singh KP, Kurzrock R, Shankar S. Sulforaphane inhibits angiogenesis through activation of FOXO transcription factors. Oncol Rep. 2009;22:1473–8.PubMed

104.

Lee SY, Moon SR. Sulforaphane inhibits ultraviolet B-induced matrix metalloproteinase expression in human dermal fibroblasts. Korean J Oriental Physiol Pathol. 2012;26:922–8.

105.

Yang MD, Lai KC, Lai TY, Hsu SC, Kuo CL, Yu CS, et al. Phenethyl isothiocyanate inhibits migration and invasion of human gastric cancer AGS cells through suppressing MAPK and NF-ΚB signal pathways. Anticancer Res. 2010;30:2135–44.PubMed

106.

Lai KC, Lu CC, Tang YJ, Chiang JH, Kuo DH, Chen FA, et al. Allyl isothiocyanate inhibits cell metastasis through suppression of the MAPK pathways in epidermal growth factor stimulated HT29 human colorectal adenocarcinoma cells. Oncol Rep. 2014;31:189–96.PubMed

107.

Masutomi N, Oyoda KT, Shibutani M, Niho N, Uneyama C, Takahashi 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;29:617–22.PubMed

108.

Okazaki K, Umemura T, Imazawa T, Nishikawa A, Masegi T, Hirose M. Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl) nitrosamine in rats after initiation. Cancer Sci. 2003;94:948–52.PubMed

109.

Ogawa K, Hirose M, Sugiura S, Cui L, Imaida K, Ogiso T, 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.PubMed

110.

Ogawa K, Futakuchi M, Hirose M, Boonyaphiphat P, Mizoguchi Y, Miki T, et al. 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. 1998;76:851–6.PubMed

111.

Sugiura S, Ogawa K, Hirose M, Takeshita F, Asamoto M, Shirai T. Reversibility of proliferative lesions and induction of non-papillary tumors in rat urinary bladder treated with phenylethyl isothiocyanate. Carcinogenesis. 2002;24:547–53.

112.

Akagi K, Sano M, Ogawa K, Hirose M, Goshima H, Shirai T. Involvement of toxicity as an early event in urinary bladder carcinogenesis induced by phenethyl isothiocyanate, benzyl isothiocyanate, and analogues in F344 rats. Toxicol Pathol. 2003;31:388–96.PubMed

113.

Langer P, Štolc V. Goitrogenic activity of allylisothiocyanate—a widespread natural mustard oil. Endocrinology. 1963;76:151–5.

114.

Heaney RK, Fenwick GR. Natural toxins and protective factors in brassica species including rapeseed. Nat Toxins. 1995;3:233–7.PubMed

115.

Shapiro TA, Fahey JW, Dinkova-Kostova AT, Holtzclaw WD, Stephenson KK, Wade KL, et al. Safety tolerance and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Nutr Cancer. 2006;55:53–62.PubMed

116.

Cartea ME, Velasco P. Glucosinolates in Brassica foods: bioavailability in food and significance for human health. Phytochem Rev. 2008;7:213–29.

117.

Kassie F, Parzefall W, Muskb S, Johnsonb I, Lamprecht C, Sontagc G, et al. Genotoxic effects of crude juices from Brassica vegetables and juices and extracts from phytopharmaceutical preparations and spices of cruciferous plants origin in bacterial and mammalian cells. Chem Biol Interact. 1996;102:1–16.PubMed

118.

Kassie F, Pool-Zobel B, Parzefall W, Knasmüller S. Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent. Mutagenesis. 1999;14:595–604.PubMed

119.

Liu H, Zhi Y, Geng G, Yu Z, Xu H. Effect of phenethyl isothiocyanate given at different duration of gestation on the outcome of pregnancy in rats. Wei Sheng Yan Jiu. 2011;40:283–6.PubMed

120.

Musk SRR, Johnson IT. The clastogenic effects of isothiocyanates. Mutat Res. 1993;300:111–7.PubMed

121.

Michaud DS, Spiegelman D, Clinton SK, Rimm EB, Willett WC, Giovannucci EL. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst. 1999;91:605–13.PubMed

122.

Feskanich D, Ziegler RG, Michaud DS, Giovannucci EL, Speizer FE, Willett WC, et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst. 2000;92:1812–23.PubMed

123.

Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC. A prospective study of cruciferous vegetables and prostate cancer. Cancer Epidemiol Biomarkers Prev. 2003;12:1403–9.PubMed

124.

Smith T, Musk SR, Johnson LT. Ally1 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.PubMed

125.

Manesh C, Kuttan G. Effect of naturally occurring allyl and phenyl isothiocyanates in the inhibition of experimental pulmonary metastasis induced by B16F-10 melanoma cells. Fitoterapia. 2003;74:355–63.PubMed

126.

Kuroiwa Y, Nishikawa A, Kitamura Y, Kanki K, Ishii Y, Umemura T, et al. Protective effects of benzyl isothiocyanate and sulforaphane but not resveratrol against initiation of pancreatic carcinogenesis in hamsters. Cancer Lett. 2006;241:275–80.PubMed

127.

Nishikawa A, Furukawa F, Uneyama C, Ikezaki S, Tanakamaru Z, Chung FL, et al. Chemopreventive effects of phenethyl isothiocyanate on lung and pancreatic tumorigenesis in N-nitrosobis (2-oxopropyl) amine treated hamsters. Carcinogenesis. 1996;17:1381–4.PubMed

128.

Solt DB, Chang KW, Helenowski I, Rademaker AW. Phenethyl isothiocyanate inhibits nitrosamine carcinogenesis in a model for study of oral cancer chemoprevention. Cancer Lett. 2003;202:147–52.PubMed

129.

130.

Conaway CC, Wang CX, Pittman B, Yang YM, Schwartz JE, Tian D, 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;65:8548–57.PubMed

131.

Takagi H, Shibutani M, Uneyama C, Lee KY, Kato N, Inoue K, et al. Limited tumor-initiating activity of phenylethyl isothiocyanate by promotion with sodium l-ascorbate in a rat two-stage urinary bladder carcinogenesis model. Cancer Lett. 2005;219:147–53.PubMed

132.

Ye B, Zhang YX, Yang F, Chen HL, Xia D, Liu MQ, et al. Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate. BMC Cancer. 2007;7:1–10.

133.

Stoner GD, Dombkowski AA, Reen RK, Cukovic D, Salagrama S, Wang LS, et al. Carcinogen-altered genes in rat esophagus positively modulated to normal levels of expression by both black raspberries and phenylethyl isothiocyanate. Cancer Res. 2008;68:6460–7.PubMedPubMedCentral

134.

Powolny AA, Bommareddy A, Hahm ER, Normolle DP, Beumer JH, Nelson JB, et al. Chemopreventative potential of the cruciferous vegetable constituent phenethyl isothiocyanate in a mouse model of prostate cancer. J Natl Cancer Inst. 2011;103:571–84.PubMedPubMedCentral

135.

Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH. Sulforaphane inhibits histone deacetylase in vivo and suppresses tumorigenesis in Apc ^min mice. FASEB J. 2006;20:506–8.PubMedPubMedCentral

136.

Dinkova-Kostova AT, Jenkins SN, Fahey JW, Ye L, Wehage SL, Liby KT, et al. Protection against UV-light-induced skin carcinogenesis in SKH-1 high-risk mice by sulforaphane-containing broccoli sprout extracts. Cancer Lett. 2006;240:243–52.PubMed

137.

Gills JJ, Jeffery EH, Matusheski NV, Moon RC, Lantvit DD, Pezzuto JM. Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion. Cancer Lett. 2006;236:72–9.PubMed

138.

Shen G, Khor TO, Hu R, Yu S, Nair S, Ho CT, et al. Chemoprevention of familial adenomatous polyposis by natural dietary compounds sulforaphane and dibenzoylmethane alone and in combination in Apc ^Min/+ mouse. Cancer Res. 2007;67:9937–44.PubMed

139.

Myzak MC, Tong P, Dashwood WM, Dashwood RH, Ho E. Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects. Exp Biol Med (Maywood). 2007;232:227–34.

140.

Matsui TA, Murata H, Sakabe T, Sowa Y, Horie N, Nakanishi R, et al. Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo. Oncol Rep. 2007;18:1263–8.PubMed

141.

Cornblatt BS, Ye L, Dinkova-Kostova AT, Erb M, Fahey JW, Singh NK, et al. Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast. Carcinogenesis. 2007;28:1485–90.PubMed

142.

Dickinson SE, Melton TF, Olson ER, Zhang J, Saboda K, Bowden GT. Inhibition of activator protein-1 by sulforaphane involves interaction with cysteine in the cFos DNA-binding domain: implications for chemoprevention of UVB-induced skin cancer. Cancer Res. 2009;69:7103–10.PubMedPubMedCentral

143.

Singh SV, Warin R, Xiao D, Powolny AA, Stan SD, Arlotti JA, et al. Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells. Cancer Res. 2009;69:2117–25.PubMedPubMedCentral

144.

Traka MH, Spinks CA, Doleman JF, Melchini A, Ball RY, Mills RD, et al. The dietary isothiocyanate sulforaphane modulates gene expression and alternative gene splicing in a PTEN null preclinical murine model of prostate cancer. Mol Cancer. 2010;9:1–23.

145.

Rausch V, Liu L, Kallifatidis G, Baumann B, Mattern J, Gladkich J, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res. 2010;70:5004–13.PubMed

146.

Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, et al. Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010;16:2580–90.PubMedPubMedCentral

147.

Priya DK, Gayathri R, Sakthisekaran D. Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo (a) pyrene. Biomed Pharmacother. 2011;65:9–16.

148.

Priya DK, Gayathri R, Gunassekaran GR, Sakthisekaran D. Protective role of sulforaphane against oxidative stress mediated mitochondrial dysfunction induced by benzo (a) pyrene in female Swiss albino mice. Pulm Pharmacol Ther. 2011;24:110–7.PubMed

Titel: Isothiocyanates: a class of bioactive metabolites with chemopreventive potential
verfasst von: Gaurav Kumar
Hardeep Singh Tuli
Sonam Mittal
Jitendra Kumar Shandilya
Anil Tiwari
Sardul Singh Sandhu
Publikationsdatum: 01.06.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 6/2015
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-3391-5

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03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Springer Medizin

Isothiocyanates: a class of bioactive metabolites with chemopreventive potential

Abstract

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Abstract

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