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Indole-3-Carbinol and Its Role in Chronic Diseases

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Anti-inflammatory Nutraceuticals and Chronic Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 928))

Abstract

Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3’-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well-recognized chemoprevention potential. Initially, these compounds were classified as blocking agents that increase drug-metabolizing enzyme activity. Now it is widely accepted that I3C and DIM affect multiple signaling pathways and target molecules controlling cell division, apoptosis, or angiogenesis deregulated in cancer cells. Although most of the current data support the role of I3C and DIM in prevention of hormone-dependent cancers, it seems that their application in prevention of the other cancer as well as cardiovascular disease, obesity, and diabetes reduction is also possible. This chapter summarizes the current experimental data on the I3C and DIM activity and the results of clinical studies indicating their role in prevention of chronic diseases.

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References

  1. Abdelrahim M, Ewman K, Vanderlaag K et al (2006) 3,3’-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis 27:717–728

    Article  CAS  PubMed  Google Scholar 

  2. Aggarwal BB, Ichikawa H (2005) Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle 4:1201–1215

    Article  CAS  PubMed  Google Scholar 

  3. Ahmad A, Sarkar WA, Rahman KMW (2011) Role of nuclear factor-kappa B signaling in anticancer properties of indole compounds. J Exp Clin Med 3:55–62

    Article  CAS  Google Scholar 

  4. Ahmad A, Biersack B, Li Y et al (2013) Targeted regulation of PI3 K/Akt/mTOR/NF-κB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy. Anticancer Agents Med Chem 13:1002–1013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Anderto MJ, Manson MM, Verschoyle RD et al (2004) Pharmacokinetics and tissue disposition of indole-3-carbinol and its acid condensation products after oral administration to mice. Clin Cancer Res 10:5233–5241

    Article  Google Scholar 

  6. Anderton MJ, Manson MM, Verschoyle R et al (2004) Physiological modeling of formulated and crystalline 3,3’-diindolylmethane pharmacokinetics following oral administration in mice. Drug Metab Dispos 32:632–638

    Article  CAS  PubMed  Google Scholar 

  7. Arora A, Seth K, Kalra N, Shukla Y (2005) Modulation of P-glycoprotein-mediated multidrug resistance in K562 leukemic cells by indole-3-carbinol. Toxicol Appl Pharmacol 202:237–243

    Article  CAS  PubMed  Google Scholar 

  8. Arora A, Shukla Y (2003) Modulation of vinca-alkaloid induced P-glycoprotein expression by indole-3-carbinol. Cancer Lett 189:167–173

    Article  CAS  PubMed  Google Scholar 

  9. Arneson DW, Hurwitz A, McMahon LM et al (1999) Presence of 3.3’-diindolylmethane in human plasma after oraladministration of indole-3-carbinol. Proc Am Assoc Cancer Res 40:429

    Google Scholar 

  10. Beaver LM, Yu TW, Sokolowski EI et al (2012) 3,3’-Diindolylmethane, but notindole-3-carbinol, inhibits histone deacetylase activity in prostate cancer cells. Toxicol Appl Pharmacol 263:345–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bell MC, Crowley-Nowick P, Bradlow HL et al (2000) Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol 78:123–129

    Article  CAS  PubMed  Google Scholar 

  12. Bhuiyan MM, Li Y, Banerjee S et al (2006) Down-regulation of androgen receptor by 3,3′-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in both hormone-sensitive LNCaP and insensitive C4-2B prostate cancer cells. Cancer Res 66:10064–10072

    Article  CAS  PubMed  Google Scholar 

  13. Bonnesen C, Eggleston IM, Hayes JD (2001) Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Cancer Res 61:6120–6130

    CAS  PubMed  Google Scholar 

  14. Bradlow HL, Michnovicz JJ, Halper M et al (1994) Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev 3:591–595

    CAS  PubMed  Google Scholar 

  15. Bradlow HL (2008) Review. Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In Vivo 22:441–445

    CAS  PubMed  Google Scholar 

  16. Bray F, Ren JS, Masuyer E et al (2013) Global estimates of cancer prevalence for 27 sites in the adult population in2008. Int J Cancer 132:1133–1145

    Article  CAS  PubMed  Google Scholar 

  17. Brait M, Sidransky D (2011) Cancer epigenetics: above and beyond. Toxicol Mech Methods 21:275–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Brew CT, Aronchik I, Hsu JC et al (2006) Indole-3-carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells. Int J Cancer 118:857–868

    Article  CAS  PubMed  Google Scholar 

  19. Chang HP, Wang ML, Hsu CY et al (2011) Supression of inflammation-associated factors by indole-3-carbinol in mice fed high-fat diets and in isolated, co-cultured macrophages and adipocytes. Int J Obes 35:1530–1538

    Article  CAS  Google Scholar 

  20. Chen DZ, Qi M, Auborn KJ et al (2001) Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplasticcervical epithelium. J Nutr 131:3294–3302

    CAS  PubMed  Google Scholar 

  21. Chen D, Banerjee S, Cui QC et al (2012) Activation of AMP-activated protein kinase by 3,3’-Diindolylmethane (DIM) is associated with human prostate cancer cell death in vitro and in vivo. PLoS ONE 7:e47186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen D, Carter TH, Auborn KJ (2004) Apoptosis in cervical cancer cells: implications for adjunct anti-estrogen therapy for cervical cancer. Anticancer Res 24:2649–2656

    CAS  PubMed  Google Scholar 

  23. Chinni SR, Li Y, Upadhyay S et al (2001) Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene 20:2927–2936

    Article  CAS  PubMed  Google Scholar 

  24. Chinni SR, Sarkar FH (2002) Akt inactivation is a key event in indole-3-carbinolinduced apoptosis in PC-3 cells. Clin Cancer Res 8:1228–1236

    CAS  PubMed  Google Scholar 

  25. Cho HJ, Park SY, Kim EJ et al (2011) 3,3′- diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model. Mol Carcinog 50:100–112

    Article  CAS  PubMed  Google Scholar 

  26. Choi Y, Kim Y, Park S et al (2012) Indole-3-carbinolprevents diet-induced obesity through modulation of multiple genes related to adipogenesis, thermogenesis or inflammation in the visceral adipose tissue of mice. J Nutr Biochem 23:1732–1739

    Article  CAS  PubMed  Google Scholar 

  27. Choi Y, Um SJ, Park T (2013) Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation. Int J Obes (Lond) 37:881–884

    Google Scholar 

  28. Christensen JG, LeBlanc GA (1996) Reversal of multidrug resistance in vivo by dietary administration of the phytochemical indole-3-carbinol. Cancer Res 56:574–581

    CAS  PubMed  Google Scholar 

  29. Cope RB, Loehr C, Dashwood R et al (2006) Ultraviolet radiation-induced non-melanoma skin cancer in the Crl:SKH1:hr-BR hairless mouse: augmentation of tumor multiplicity by chlorophyllin and protection by indole-3-carbinol. Photochem Photobiol Sci 5(5):499–507

    Article  CAS  PubMed  Google Scholar 

  30. Cover MC, Hsieh SJ, Tran SH et al (1998) Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling. J Biol Chem 273:3838–3847

    Article  CAS  PubMed  Google Scholar 

  31. Cover CM, Hsieh SJ, Cram EJ et al (1999) Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res 59:1244–1251

    CAS  PubMed  Google Scholar 

  32. Cram EJ, Liu BD, Bjeldanes LF et al (2001) Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter. J Biol Chem 276:22332–22340

    Article  CAS  PubMed  Google Scholar 

  33. Dalessandri KM, Firestone GL, Fitch MD et al (2004) Pilot study: effect of 3, 3′-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer 50:161–167

    Article  CAS  PubMed  Google Scholar 

  34. Dashwood RH, Fong AT, Arbogast DN et al (1994) Anticarcinogenic activity of indole-3-carbinol acid products: ultrasensitive bioassay by trout embryo microinjection. Cancer Res 54:3617–3619

    CAS  PubMed  Google Scholar 

  35. Dashwood RH (1998) Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact 110:1–5

    Article  CAS  PubMed  Google Scholar 

  36. Deng W, Zong J, Bian Z et al (2013) Indole-3-carbinolprotects against pressure overload induced cardiac remodeling via activating AMPK-α. Mol Nutr Food Res 57:1680–1687

    Article  CAS  PubMed  Google Scholar 

  37. Denis LJ, Griffiths K (2000) Endocrine treatment in prostate cancer. Semin Surg Oncol 18:52–74

    Article  CAS  PubMed  Google Scholar 

  38. de Bilderling G, Bodart E, Lawson G et al (2005) Successful use of intralesional and intravenous Cidofovir in association withindole-3-carbinol in an 8-year-old girl with pulmonary papillomatosis. J Med Virol 75:332–335

    Article  PubMed  Google Scholar 

  39. De Kruif CA, Marsman JW, Venekamp JC et al (1991) Structure elucidation of acid reaction products of indole-3-carbinol: detection in vivo and enzyme induction in vitro. Chem Biol Interact 80:303–315

    Article  PubMed  Google Scholar 

  40. Del Priore G, Gudipudi DK, Montemarano N et al (2010) Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervicaldysplasia. Gynecol Oncol 116:464–467

    Article  PubMed  CAS  Google Scholar 

  41. Donald S, Verschoyle RD, Greaves P et al (2004) Dietary agent indole-3-carbinol protects female rats against the hepatotoxicity of the antitumor drug ET-743 (trabectidin) without compromising efficacy in a rat mammary carcinoma. Int J Cancer 111:961–967

    Article  CAS  PubMed  Google Scholar 

  42. Dunn SE, LeBlanc GA (1994) Hypocholesterolemic properties of plant indoles. Inhibition of acyl-CoA:cholesterol acyltransferase activity and reduction of serum LDL/VLDL cholesterol levels by glucobrassicin derivatives. BiochemPharmacol 47:359–364

    CAS  Google Scholar 

  43. Dzau VJ, Braun-Dullaeus RC, Sedding DG (2002) Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med 8:1249–1256

    Article  CAS  PubMed  Google Scholar 

  44. Fan S, Meng Q, Auborn K et al (2006) BRCA1 and BRCA2 as molecular targets for phytochemicals indole-3-carbinol and genistein in breast and prostate cancer cells. Br J Cancer 94:407–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fares F (2014) The anti-carcinogenic effect of indole-3-carbinol and 3,3’-diindolylmethane and mechanism of action. Med Chem. doi:10.4172/2161-0444.S1-002

    Google Scholar 

  46. Fuentes F, Paredes-Gonzalez X, Kong AT (2015) Dietary glucosinolates sulforaphane, phenethyl isothiocyanate, indole-3-carbinol/3,3’-diindolylmethane: anti-oxidative stress/inflammation, nrf2, epigenetics/epigenomics and in vivo cancer chemopreventive efficacy. Curr Pharmacol Rep 1:179–196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fujioka N, Ainslie-Waldman CE, Upadhyaya P et al (2014) Urinary 3,3′-diindolylmethane: a biomarker of glucobrassicin exposure and indole-3-carbinol uptake in humans. Cancer Epidemiol Biomark Prev 23:282–287

    Article  CAS  Google Scholar 

  48. Garcia HH, Brar GA, Nguyen DH et al (2005) Indole-3-Carbinol (I3C) inhibits cyclin-dependent kinase-2 function in human breast cancer cells by regulating the size distribution, associated cyclin E forms, and subcellular localization of the CDK2 protein complex. J Biol Chem 280:8756–8764

    Article  CAS  PubMed  Google Scholar 

  49. Garikapaty VP, Ashok BT, Chen YG et al (2005) Anti-carcinogenic and anti-metastatic properties of indole-3-carbinol in prostate cancer. Oncol Rep 13:89–93

    CAS  PubMed  Google Scholar 

  50. Ge X, Fares FA, Yannai S (1999) Induction of apoptosis in MCF-7 cells by indole-3-carbinol is independent of p53 and bax. Anticancer Res 19:3199–3203

    CAS  PubMed  Google Scholar 

  51. Guan H, Chen C, Zhu L et al (2013) Indole-3-carbinolblocks platelet-derived growth factor-stimulated vascular smooth muscle cell function and reduces neointima formation in vivo. J NutrBiochem 24:62–69

    CAS  Google Scholar 

  52. Hayes JD, Dinkova-Kostova AT, McMahon M (2009) Cross-talk between transcription factors AhR and Nrf2: lessons for cancer chemoprevention from dioxin. Toxicol Sci 111:199–201

    Article  CAS  PubMed  Google Scholar 

  53. Heath EI, Heilbrun LK, Li J (2010) Phase I dose-escalation study of oral BR-DIM (BioResponse 3,3′- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am J Transl Res 2:402–411

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Heinlein CA, Chang C (2004) Androgen receptor in prostate cancer. Endocr Rev 25:276–308

    Article  CAS  PubMed  Google Scholar 

  55. Hong C, Kim HA, Firestone GL et al (2002) 3,3’-Diindolylmethane (DIM) induces a G(1) cell cycle arrest in human breast cancer cells that is accompanied by Sp1-mediated activation of p21(WAF1/CIP1) expression. Carcinogenesis 23:1297–1305

    Article  CAS  PubMed  Google Scholar 

  56. Horn TL, Reichert MA, Bliss RL (2002) Modulations of P450 mRNA in liver and mammary gland and P450 activities and metabolism of estrogen in liver by treatment of rats with indole-3-carbinol. Biochem Pharmacol 64:393–404

    Article  CAS  PubMed  Google Scholar 

  57. Hwang JW, Jung JW, Lee YS et al (2008) Indole-3-carbinol prevents H(2)O(2)-induced inhibition of gap junctional intercellular communication by inactivation of PKB/Akt. J Vet Med Sci 70:1057–1063

    Article  CAS  PubMed  Google Scholar 

  58. International Agency for Research on Cancer (1999) Monographs on the evolution of carcinogenic risks to humans: hormonal contraception and postmenopausal hormone therapy, vol 72. IARC, Lyon, France

    Google Scholar 

  59. Izzotti A, Calin GA, Steele VE et al (2010) Chemoprevention of cigarette smoke-induced alterations of microRNA expression in rat lungs. Cancer Prev Res 3:62–72

    Article  CAS  Google Scholar 

  60. Jayakumar P, Pugalendi KV, Sankaran M (2014) Attenuation of hyperglycemia-mediated oxidative stress by indole-3-carbinol and its metabolite 3, 3’- diindolylmethane in C57BL/6 J mice. J Physiol Biochem 70:525–534

    Article  CAS  PubMed  Google Scholar 

  61. Jin L, Qi M, Chen DZ et al (1999) Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice. Cancer Res 59:3991–3997

    CAS  PubMed  Google Scholar 

  62. Jin Y (2011) 3,3’-Diindolylmethane inhibits breast cancer cell growth via miR-21-mediated Cdc25A degradation. Mol Cell Biochem 358:345–354

    Article  CAS  PubMed  Google Scholar 

  63. Kassie F, Anderson LB, Scherber R et al (2007) Indole-3-carbinol inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone plus benzo(a)pyrene-induced lung tumorigenesis in A/J mice and modulates carcinogen-induced alterations in protein levels. Cancer Res 67:6502–6511

    Article  CAS  PubMed  Google Scholar 

  64. Kassie F, Kalscheuer S, Matise I et al (2010) Inhibition of vinyl carbamate-induced pulmonary adenocarcinoma by indole-3-carbinol and myo-inositol in A/J mice. Carcinogenesis 31:239–245

    Article  CAS  PubMed  Google Scholar 

  65. Kassie F, Melkamu T, Endalew A et al (2010) Inhibition of lungcarcinogenesis and critical cancer-related signaling pathways by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-l-cysteine, indole-3-carbinol and myo-inositol, alone and in combination. Carcinogenesis 31:1634–1641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kim DJ, Han BS, Ahn B et al (1997) Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model. Carcinogenesis 18:377–381

    Google Scholar 

  67. Kim EJ, Park Sy, Shin et al (2007) Activation of caspase-8 contributes to 3,3’-Diindolylmethane-induced apaptosis in colon cancer cells. J Nutr 137:31–36

    Google Scholar 

  68. Kojima T, Tanaka T, Mori H (1994) Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res 54:1446–1449

    CAS  PubMed  Google Scholar 

  69. Kong D, Heath E, Chen W et al (2012) Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS ONE 7:e33729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kong D, Heath E, Chen W et al (2012) Epigenetic silencing of miR-34a in human prostate cancer cells and tumor tissue specimens can be reversed by BR-DIM treatment. Am J Transl Res 4:14–23

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Kumi-Diaka J, Merchant K, Haces A et al (2010) Genistein-selenium combination induces growth arrest in prostate cancer cells. J Med Food 13:842–850

    Article  CAS  PubMed  Google Scholar 

  72. Kumar MM, Davuluri S, Poojar S et al (2015) Role of estrogen receptor alpha in human cervical cancer-associated fibroblasts: a transcriptomic study. Tumour Biol Oct 24 [Epub ahead of print]

    Google Scholar 

  73. Lawrence T (2009) The nuclear factor NF-κB pathway in Inflammation. Cold Spring Harb Perspect Biol 1:a001651. doi:10.1101/cshperspect.a001651

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Le HT, Schaldach CM, Firestone GL et al (2003) Plant-derived 3,3’-Diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem 278:21136–21145

    Article  CAS  PubMed  Google Scholar 

  75. Leong H, Riby JE, Firestone GL et al (2004) Potent ligand-independent estrogen receptor activation by 3,3′-diindolylmethane is mediated by cross talk between the protein kinase A and mitogen-activated protein kinase signaling pathways. Mol Endocrinol 18:291–302

    Article  CAS  PubMed  Google Scholar 

  76. Li Y, Li X, Sarkar FH (2003) Gene expression profiles of I3C- and DIM-treated PC3 human prostate cancer cells determined by cDNA microarray analysis. J Nutr 133:1011–1019

    CAS  PubMed  Google Scholar 

  77. Li Y, Wang Z, Kong D et al (2007) Regulation of FOXO3a/beta-catenin/GSK-3beta signaling by 3,3’-diindolylmethane contributes to inhibition of cell proliferation and induction of apoptosis in prostate cancer cells. J Biol Chem 282:21542–21550

    Article  CAS  PubMed  Google Scholar 

  78. Li Y, VandenBoomII TG, Wang Z et al (2010) miRNA146a suppresses invasion of pancreatic cancer cells. Cancer Res 70:1486–1495

    Google Scholar 

  79. Lian JP, Word B, Taylor S et al (2004) Modulation of the constitutive activated STAT3 transcription factor in pancreatic cancer prevention: effects of indole-3-carbinol (I3C) and genistein. Anticancer Res 24:133–137

    Google Scholar 

  80. Licznerska BE, Szaefer H, Murias M et al (2013) Modulation of CYP19 expression by cabbage juices and their active components: indole-3-carbinol and 3,3’-diindolylmethane in human breast epithelial cell lines. Eur J Nutr 52:1483–1492

    Article  CAS  PubMed  Google Scholar 

  81. Lo R, Matthews J (2013) The aryl hydrocarbon receptor and estrogen receptoralpha differentially modulate nuclear factor erythroid-2-related factor2 transactivation in MCF-7 breast cancer cells. Toxicol Appl Pharmacol 270:139–148

    Article  CAS  PubMed  Google Scholar 

  82. Lu Q, Nakmura J, Savinov A et al (1996) Expression of aromatase protein and messenger ribonucleic acid in tumor epithelial cells and evidence of functional significance of locally produced estrogen in human breast cancer. Endocrinology 137:3061–3068

    CAS  PubMed  Google Scholar 

  83. Luo J, Manning BD, Cantley LC (2003) Targeting the PI3 K-Akt pathway in human cancer: rationale andpromise. Cancer Cell 4:257–262

    Article  CAS  PubMed  Google Scholar 

  84. Lynn A, Collins A, Fuller Z et al (2006) Cruciferous vegetables and colorectal cancer. Proc Nutr Soc 65:135–144

    Article  CAS  PubMed  Google Scholar 

  85. Maiyoh GK, Kuh JE, Casaschi A et al (2007) Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells. J Nutr 137:2185–2189

    CAS  PubMed  Google Scholar 

  86. Marconett CN, Singhal AK, Sundar SN et al (2012) Indole-3-carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells. Mol Cell Endocrinol 363:74–84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. McGuire KP, Ngoubilly N, Neavyn M et al (2006) 3,3′-diindolylmethane and paclitaxel act synergistically to promote apoptosis in HER2/Neu human breast cancer cells. J Surg Res 132:208–213

    Article  CAS  PubMed  Google Scholar 

  88. Melkamu T, Zhang X, Tan J et al (2010) Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol. Carcinogenesis 31:252–258

    Article  CAS  PubMed  Google Scholar 

  89. Meng Q, Qi M, Chen DZ et al (2000) Suppression of breast cancer invasion and migration by indole-3-carbinol: associated with up-regulation of BRCA1 and E-cadherin/catenin complexes. J Mol Med 78:155–165

    Article  CAS  PubMed  Google Scholar 

  90. Mesnil M, Crespin S, Avanzo JL et al (2005) Defective gap junctional intercellular communication in the carcinogenic process. Biochim Biophys Acta 1719:125–145

    Article  CAS  PubMed  Google Scholar 

  91. Michnovicz JJ, Adlercreutz H, Bradlow HL (1997) Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst 89:718–723

    Article  CAS  PubMed  Google Scholar 

  92. Mulvey L, Chandrasekaran A, Liu K et al (2007) Interplay of genes regulated by estrogen and diindolylmethane in breast cancer cell lines. Mol Med 13:69–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nakamura Y, Yogosawa S, Izutani Y et al (2009) A combination of indol-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Aktphosphorylation and progression of autophagy. Mol Cancer 8:100. doi:10.1186/1476-4598-8-100

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Nachshon-Kedmi M, Yannai S, Haj A et al (2003) Indole-3-carbinol and 3,3’-diindolylmethane induce apoptosis in human prostate cancer cells. Food Chem Toxicol 41:745–752

    Article  CAS  PubMed  Google Scholar 

  95. Oganesian A, Hendricks JD, Williams DE (1997) Long term dietary indole-3-carbinol inhibits diethylnitrosamine-initiated hepatocarcinogenesis in the infant mouse model. Cancer Lett 118:87–94

    Article  CAS  PubMed  Google Scholar 

  96. Ohtake F, Fujii-Kuriyama Y, Kawajiri K et al (2011) Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system. J Steroid Biochem Mol Biol 127:102–107

    Article  CAS  PubMed  Google Scholar 

  97. Pagliaro B, Santolamazza C, Simonelli F et al (2015) Phytochemical compounds and protection from cardiovascular diseases: a state of the art. BioMed Res Int. doi:10.1155/2015/918069

    Google Scholar 

  98. Paik WH, Kim HR, Park JK et al (2013) Chemosensitivity induced by down-regulation of MicroRNA-21 in gemcitabine-resistant pancreatic cancer cells by indole-3-carbinol. Anticancer Res 33:1473–1482

    CAS  PubMed  Google Scholar 

  99. Park MK, Rhee YH, Lee HJ et al (2008) Antiplatelet and antithrombotic activity of indole-3-carbinolin vitro and in vivo. Phytother Res 22:58–64

    Article  CAS  PubMed  Google Scholar 

  100. Pearson G, Robinson F, Beers Gibson T et al (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22:153–183

    CAS  PubMed  Google Scholar 

  101. Penning TM, Burczynski ME, Jez JM et al (2000) Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones. Biochem J 351:67–77

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Qian X, Melkamu T, Upadhyaya P et al (2011) Indole-3-carbinol inhibited tobacco smokecarcinogen-induced lung adenocarcinoma in A/J mice when administered during the post-initiation or progression phase of lung tumorigenesis. Cancer Lett 311:57–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Rahman KM, Aranha O, Sarkar FH (2003) Indole-3-carbinol (I3C) induces apoptosis in tumorigenic but not in nontumorigenic breast epithelial cells. Nutr Cancer 45:101–112

    Article  CAS  PubMed  Google Scholar 

  104. Rajoria S, Suriano R, Parmar PS et al (2011) 3,3’-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid 21:299–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Reed GA, Peterson KS, Smith HJ et al (2005) A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomark Prev 14:1953–1960

    Article  CAS  Google Scholar 

  106. Rice JC, Ozcelik H, Maxeiner P et al (2000) Methylation of the BRCA1 promoter is associated with decreased BRCA1 mRNA levels in clinical breast cancer specimens. Carcinogenesis 21:1761–1765

    Article  CAS  PubMed  Google Scholar 

  107. Rosen CA, Woodson GE, Thompson JW et al (1998) Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 118:810–815

    Article  CAS  PubMed  Google Scholar 

  108. Rosen CA, Bryson PC (2004) Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J Voice 18:248–253

    Google Scholar 

  109. Sarkar FH, Li Y, Wang Z et al (2009) Cellular signaling perturbation by natural products. Cell Signal 21:1541–1547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Sarkar FH, Li Y (1997) Indole-3-carbinol and prostate cancer. J Nutr 134:3493S–3498S

    Google Scholar 

  111. Sarkar S, Dubaybo H, Ali S et al (2013) Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27(kip1), p57(kip2), and PUMA.Am. J Cancer Res 3:465–477

    Google Scholar 

  112. Shaw RJ, Cantley LC (2006) Ras, PI(3)K and mTORsignalling controls tumour cell growth. Nature 441:424–430

    Article  CAS  PubMed  Google Scholar 

  113. Singhal R, Shankar K, Badger TM et al (2008) Estrogenic status modulatesaryl hydrocarbon receptor-mediated hepatic gene expression andcarcinogenicity. Carcinogenesis 29:227–236

    Article  CAS  PubMed  Google Scholar 

  114. Szaefer H, Krajka-Kuźniak V, Licznerska B (2015) Cabbage juices and indoles modulate the expression profile of AhR, ERα, and Nrf2 in human breast cell lines. Nutr Cancer 67:1342–1345

    Article  PubMed  CAS  Google Scholar 

  115. Śmiechowska A, Bartoszek A, Namieśnik J (2008) Cancer chemopreventive agents: Glucosinolates and their decomposition products in white cabbage (Brassica oleracea var. Capitata). Postepy Hig Med Dosw (online) 62:125–140

    Google Scholar 

  116. Tadi K, Chang Y, Ashok BT et al (2005) 3,3’-Diidolylmethane, a cruciferous vegetable derived synthetic antiprolifereative compound in thyroid disease. Biochem Biophys Res Commun 337:1019–1025

    Article  CAS  PubMed  Google Scholar 

  117. Terry P, Wolk A, Persson I et al (2001) Brassica vegetables and breast cancer risk. JAMA 285:2975–2977

    Article  CAS  PubMed  Google Scholar 

  118. van Poppel G, Verhoeven DT, Verhagen H et al (1999) Brassica vegetables and cancer prevention. Epidemiology and mechanisms. Adv Exp Med Biol 472:159–168

    Article  PubMed  Google Scholar 

  119. Vahid F, Zand H, Nosrat-Mirshekarlou E et al (2015) The role dietary of bioactivecompounds on the regulation of histone acetylases and deacetylases: a review. Gene 562:8–15

    Article  CAS  PubMed  Google Scholar 

  120. Vang O (2006) Chemopreventive potential of compounds in Cruciferous vegetables. In: Baer-Dubowska W, Bartoszek A, Malejka-Giganti D (eds) Carcinogenic and anticarcinogenic food components. CRC Taylor & Francis, Boca Raton, pp 303–328

    Google Scholar 

  121. Verhagen H, Poulsen HE, Loft S et al (1995) Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis 16:969–970

    Article  CAS  PubMed  Google Scholar 

  122. Wattenberg LW, Loub WD (1978) Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 38:1410–1413

    CAS  PubMed  Google Scholar 

  123. Wattenberg LW, Loub WD, Lam LK, Speier JL (1976) Dietary constituents altering the responses to chemical carcinogens. Fed Proc 35:1327–1331

    CAS  PubMed  Google Scholar 

  124. Wattenberg LW, Hanley AB, Barany G et al (1985) Inhibition of carcinogenesis by some minor dietary constituents. Princess Takamatsu Symp 16:193–203

    CAS  PubMed  Google Scholar 

  125. WHO Report Part II 2015

    Google Scholar 

  126. Wilson CA, Ramos L, Villaseñor MR et al (1999) Localization of human BRCA1 and its loss in high-grade, non-inherited breast carcinomas. Nat Genet 21:236–240

    Article  CAS  PubMed  Google Scholar 

  127. Witter DC, Le Bas J (2008) Cancer as a chronic disease. Oncology 53:1–3

    Google Scholar 

  128. Wong GY, Bradlow L, Sepkovic D et al (1997) Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl 28–29:111–116

    Article  Google Scholar 

  129. Wong CP, Hsu A, Buchanan A et al (2014) Effects of sulforaphane and 3,3′-diindolylmethane on genome-wide promoter methylation in normalprostate epithelial cells and prostate cancer cells. PLoS ONE 9:e86787. doi:10.1371/journal.pone.0086787

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Wu TY, Khor TO, Su ZY et al (2013) Epigenetic modifications of Nrf2 by 3,3′-diindolylmethanein vitro in TRAMP C1 cell line and in vivo TRAMP prostate tumors. AAPS J 15:864–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Xu M, Orner GA, Bailey GS et al (2001) Post-initiation effects of chlorophyllin and indole-3-carbinol in rats given 1,2-dimethylhydrazine or 2-amino-3- methylimidazo[4, 5-f]quinoline. Carcinogenesis 22:309–314

    Article  CAS  PubMed  Google Scholar 

  132. Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Yoshida M, Katashima S, Ando J et al (2004) Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N-ethyl-N’-nitro-N-nitrosoguanidine, with induction of cytochrome P450 s in the liver and consequent modulation of estrogen metabolism. Carcinogenesis 25:2257–2264

    Article  CAS  PubMed  Google Scholar 

  134. Zhang J, Hsu BAJC, Kinseth BAMA et al (2003) Indole-3-carbinol induces a G1 cell cycle arrest and inhibits prostate-specificantigen production in human LNCaP prostate carcinoma cells. Cancer 98:2511–2520

    Article  CAS  PubMed  Google Scholar 

  135. Zhu J, Li Y, Guan C et al (2012) Anti-proliferative and pro-apoptotic effects of 3, 3’-diindolylmethane in human cervical cancer cells. Oncol Rep 28:1063–1068

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznan, Poland

    Barbara Licznerska & Wanda Baer-Dubowska

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  1. Barbara Licznerska
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  2. Wanda Baer-Dubowska
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Correspondence to Wanda Baer-Dubowska .

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  1. Banaras Hindu University , Varanasi, Uttar Pradesh, India

    Subash Chandra Gupta

  2. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

    Sahdeo Prasad

  3. Anti-Inflammation Research Institute, San Diego, California, USA

    Bharat B. Aggarwal

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Licznerska, B., Baer-Dubowska, W. (2016). Indole-3-Carbinol and Its Role in Chronic Diseases. In: Gupta, S., Prasad, S., Aggarwal, B. (eds) Anti-inflammatory Nutraceuticals and Chronic Diseases. Advances in Experimental Medicine and Biology, vol 928. Springer, Cham. https://doi.org/10.1007/978-3-319-41334-1_6

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