1932

Abstract

Indole-3-carbinol (I3C) is a bioactive phytochemical abundant in cruciferous vegetables. One of its main in vivo metabolites is 3,3′-diindolylmethane (DIM), formed by the condensation of two molecules of I3C. Both I3C and DIM alter multiple signaling pathways and related molecules controlling diverse cellular events, including oxidation, inflammation, proliferation, differentiation, apoptosis, angiogenesis, and immunity. There is a growing body of evidence from both in vitro and in vivo models that these compounds possess strong potential to prevent several forms of chronic disease such as inflammation, obesity, diabetes, cardiovascular disease, cancer, hypertension, neurodegenerative diseases, and osteoporosis. This article reviews current knowledge of the occurrence of I3C in nature and foods, along with the beneficial effects of I3C and DIM concerning prevention and treatment of human chronic diseases, focusing on preclinical studies and their mechanisms of action at cellular and molecular levels.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-food-060721-025531
2023-03-27
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/food/14/1/annurev-food-060721-025531.html?itemId=/content/journals/10.1146/annurev-food-060721-025531&mimeType=html&fmt=ahah

Literature Cited

  1. Adler S, Rashid G, Klein A. 2011. Indole-3-carbinol inhibits telomerase activity and gene expression in prostate cancer cell lines. Anticancer Res. 31:3733–37
    [Google Scholar]
  2. Agerbirk N, De Vos M, Kim JH, Jander G. 2009. Indole glucosinolate breakdown and its biological effects. Phytochem. Rev. 8:101–20
    [Google Scholar]
  3. Agerbirk N, Olsen CE. 2012. Glucosinolate structures in evolution. Phytochemistry 77:16–45
    [Google Scholar]
  4. Ampofo E, Lachnitt N, Rudzitis-Auth J, Schmitt BM, Menger MD, Laschke MW. 2017. Indole-3-carbinol is a potent inhibitor of ischemia-reperfusion-induced inflammation. J. Surg. Res. 215:34–46
    [Google Scholar]
  5. Ampofo E, Schmitt BM, Menger MD, Laschke MW. 2018. Targeting the microcirculation by indole-3-carbinol and its main derivate 3,3,′-diindolylmethane: effects on angiogenesis, thrombosis and inflammation. Mini Rev. Med. Chem. 18:962–68
    [Google Scholar]
  6. Barrett JE, Klopfenstein CF, Leipold HW. 1998. Protective effects of cruciferous seed meals and hulls against colon cancer in mice. Cancer Lett. 127:83–88
    [Google Scholar]
  7. Bennett RN, Mellon FA, Kroon PA. 2004. Screening crucifer seeds as sources of specific intact glucosinolates using ion-pair high-performance liquid chromatography negative ion electrospray mass spectrometry. J. Agric. Food Chem. 52:428–38
    [Google Scholar]
  8. Bodnaryk R, Yoshihara T. 1995. Structure-activity relationships of cyclopentane analogs of jasmonic acid for induced responses of canola seedlings, Brassica napus L. J. Chem. Ecol. 21:1735–43
    [Google Scholar]
  9. Brandt JZ, Silveira LT, Grassi TF, Anselmo-Franci JA, Fávaro WJ et al. 2014. Indole-3-carbinol attenuates the deleterious gestational effects of bisphenol A exposure on the prostate gland of male F1 rats. Reprod. Toxicol. 43:56–66
    [Google Scholar]
  10. Brew CT, Aronchik I, Kosco K, McCammon J, Bjeldanes LF, Firestone GL. 2009. Indole-3-carbinol inhibits MDA-MB-231 breast cancer cell motility and induces stress fibers and focal adhesion formation by activation of Rho kinase activity. Int. J. Cancer 124:2294–302
    [Google Scholar]
  11. Brown PD, Tokuhisa JG, Reichelt M, Gershenzon J. 2003. Variation of glucosinolate accumulation among different organs and developmental stages of Arabidopsis thaliana. Phytochemistry 62:471–81
    [Google Scholar]
  12. Burow M, Losansky A, Müller R, Plock A, Kliebenstein DJ, Wittstock U. 2009. The genetic basis of constitutive and herbivore-induced ESP-independent nitrile formation in Arabidopsis. Plant Physiol. 149:561–74
    [Google Scholar]
  13. Busbee PB, Menzel L, Alrafas HR, Dopkins N, Becker W et al. 2020. Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22-dependent manner. JCI Insight 5:1e127551
    [Google Scholar]
  14. Buskov S, Olsen CE, Sørensen H, Sørensen S. 2000. Supercritical fluid chromatography as basis for identification and quantitative determination of indol-3-ylmethyl oligomers and ascorbigens. J. Biochem. Biophys. Methods 43:175–95
    [Google Scholar]
  15. Cartea ME, Velasco P, Obregón S, Padilla G, de Haro A. 2008. Seasonal variation in glucosinolate content in Brassica oleracea crops grown in northwestern Spain. Phytochemistry 69:403–10
    [Google Scholar]
  16. Caruso JA, Campana R, Wei C, Su CH, Hanks AM et al. 2014. Indole-3-carbinol and its N-alkoxy derivatives preferentially target ERα-positive breast cancer cells. Cell Cycle 13:2587–99
    [Google Scholar]
  17. Chang HP, Wang ML, Chan MH, Chiu YS, Chen YH. 2011. Antiobesity activities of indole-3-carbinol in high-fat-diet-induced obese mice. Nutrition 27:463–70
    [Google Scholar]
  18. Chang HP, Wang ML, Hsu CY, Liu ME, Chan MH, Chen YH. 2011. Suppression 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. 35:1530–38
    [Google Scholar]
  19. Chang X, Tou JC, Hong C, Kim HA, Riby JE et al. 2005. 3,3′-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis 26:771–78
    [Google Scholar]
  20. Cho HJ, Seon MR, Lee YM, Kim J, Kim JK et al. 2008. 3,3′-Diindolylmethane suppresses the inflammatory response to lipopolysaccharide in murine macrophages. J. Nutr. 138:17–23
    [Google Scholar]
  21. Choi HJ, Lim DY, Park JH. 2009. Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3′-diindolylmethane in HT-29 human colon cancer cells. BMC Gastroenterol. 9:39
    [Google Scholar]
  22. Choi KM, Yoo HS. 2018. 3,3′-Diindolylmethane enhances glucose uptake through activation of insulin signaling in 3T3-L1 adipocytes. Obesity 26:1153–60
    [Google Scholar]
  23. Choi KM, Yoo HS. 2019. Amelioration of hyperglycemia-induced nephropathy by 3,3′-diindolylmethane in diabetic mice. Molecules 24:4474
    [Google Scholar]
  24. Choi Y, Abdelmegeed MA, Song BJ. 2018. Preventive effects of indole-3-carbinol against alcohol-induced liver injury in mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: role of gut-liver-adipose tissue axis. J. Nutr. Biochem. 55:12–25
    [Google Scholar]
  25. Choi Y, Kim Y, Park S, Lee KW, Park T. 2012. Indole-3-carbinol prevents diet-induced obesity through modulation of multiple genes related to adipogenesis, thermogenesis or inflammation in the visceral adipose tissue of mice. J. Nutr. Biochem. 23:1732–39
    [Google Scholar]
  26. Choi Y, Um SJ, Park T. 2013. Indole-3-carbinol directly targets SIRT1 to inhibit adipocyte differentiation. Int. J. Obes. 37:881–84
    [Google Scholar]
  27. Ciska E, Pathak DR. 2004. Glucosinolate derivatives in stored fermented cabbage. J. Agric. Food Chem. 52:7938–43
    [Google Scholar]
  28. Ciska E, Verkerk R, Honke J. 2009. Effect of boiling on the content of ascorbigen, indole-3-carbinol, indole-3-acetonitrile, and 3,3′-diindolylmethane in fermented cabbage. J. Agric. Food Chem. 57:2334–38
    [Google Scholar]
  29. Connolly EL, Sim M, Travica N, Marx W, Beasy G et al. 2021. Glucosinolates from cruciferous vegetables and their potential role in chronic disease: investigating the preclinical and clinical evidence. Front. Pharmacol. 12:767975
    [Google Scholar]
  30. Cunningham MW Jr., Sasser JM, West CA, Milani CJ, Baylis C, Mitchell KD. 2013. Renal nitric oxide synthase and antioxidant preservation in Cyp1a1-Ren-2 transgenic rats with inducible malignant hypertension. Am. J. Hypertens. 26:1242–49
    [Google Scholar]
  31. El-Daly SM, Gamal-Eldeen AM, Gouhar SA, Abo-Elfadl MT, El-Saeed G. 2020. Modulatory effect of indoles on the expression of miRNAs regulating G1/S cell cycle phase in breast cancer cells. Appl. Biochem. Biotechnol. 192:1208–23
    [Google Scholar]
  32. El-Naga RN, Mahran YF 2016. Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1. Sci. Rep. 6:29857
    [Google Scholar]
  33. Fahey JW, Zalcmann AT, Talalay P. 2001. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 56:5–51
    [Google Scholar]
  34. Fahey JW, Zhang Y, Talalay P. 1997. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. PNAS 94:10367–72
    [Google Scholar]
  35. Hajra S, Patra AR, Basu A, Saha P, Bhattacharya S. 2018. Indole-3-carbinol (I3C) enhances the sensitivity of murine breast adenocarcinoma cells to doxorubicin (DOX) through inhibition of NF-κβ, blocking angiogenesis and regulation of mitochondrial apoptotic pathway. Chem. Biol. Interact. 290:19–36
    [Google Scholar]
  36. Halkier BA, Gershenzon J. 2006. Biology and biochemistry of glucosinolates. Annu. Rev. Plant Biol. 57:303–33
    [Google Scholar]
  37. Hanschen FS, Lamy E, Schreiner M, Rohn S. 2014. Reactivity and stability of glucosinolates and their breakdown products in foods. Angew. Chem. Int. Ed. 53:11430–50
    [Google Scholar]
  38. Holst B, Williamson G. 2004. A critical review of the bioavailability of glucosinolates and related compounds. Nat. Prod. Rep. 21:425–47
    [Google Scholar]
  39. 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/6J mice. J. Physiol. Biochem. 70:525–34
    [Google Scholar]
  40. Jeon EJ, Davaatseren M, Hwang JT, Park JH, Hur HJ et al. 2016. Effect of oral administration of 3,3′-diindolylmethane on dextran sodium sulfate-induced acute colitis in mice. J. Agric. Food Chem. 64:7702–9
    [Google Scholar]
  41. Jiang J, Kang TB, Shim DW, Oh NH, Kim TJ, Lee KH. 2013. Indole-3-carbinol inhibits LPS-induced inflammatory response by blocking TRIF-dependent signaling pathway in macrophages. Food Chem. Toxicol. 57:256–61
    [Google Scholar]
  42. Jiang Y, Yang G, Liao Q, Zou Y, Du Y, Huang J. 2019. Indole-3-carbinol inhibits lipid deposition and promotes autophagy in hyperlipidemia zebrafish larvae. Environ. Toxicol. Pharmacol. 70:103205
    [Google Scholar]
  43. Jump SM, Kung J, Staub R, Kinseth MA, Cram EJ et al. 2008. N-Alkoxy derivatization of indole-3-carbinol increases the efficacy of the G1 cell cycle arrest and of I3C-specific regulation of cell cycle gene transcription and activity in human breast cancer cells. Biochem. Pharmacol. 75:713–24
    [Google Scholar]
  44. Kandala PK, Srivastava SK. 2010. Activation of checkpoint kinase 2 by 3,3′-diindolylmethane is required for causing G2/M cell cycle arrest in human ovarian cancer cells. Mol. Pharmacol. 78:297–309
    [Google Scholar]
  45. Katz E, Nisani S, Chamovitz DA. 2018. Indole-3-carbinol: a plant hormone combatting cancer. F1000Research 7:689
    [Google Scholar]
  46. Khan AS, Langmann T. 2020. Indole-3-carbinol regulates microglia homeostasis and protects the retina from degeneration. J. Neuroinflammation 17:327
    [Google Scholar]
  47. Kim EJ, Park H, Kim J, Park JH 2010. 3,3′-Diindolylmethane suppresses 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin via the downregulation of inflammatory mediators. Mol. Carcinog. 49:672–83
    [Google Scholar]
  48. Kim EJ, Park SY, Shin HK, Kwon DY, Surh YJ, Park JH. 2007. Activation of caspase-8 contributes to 3,3′-diindolylmethane-induced apoptosis in colon cancer cells. J. Nutr. 137:31–36
    [Google Scholar]
  49. Kim EJ, Shin M, Park H, Hong JE, Shin HK et al. 2009. Oral administration of 3,3′-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. J. Nutr. 139:2373–79
    [Google Scholar]
  50. Kim EK, Kim YS, Milner JA, Wang TT. 2013. Indole-3-carbinol and 3′,3′-diindolylmethane modulate androgen's effect on C-C chemokine ligand 2 and monocyte attraction to prostate cancer cells. Cancer Prev. Res. 6:519–29
    [Google Scholar]
  51. Kim HW, Kim J, Lee S, Choi BR, Han JS et al. 2014. 3,3′-Diindolylmethane inhibits lipopolysaccharide-induced microglial hyperactivation and attenuates brain inflammation. Toxicol. Sci. 137:158–67
    [Google Scholar]
  52. Kim JH, Jander G. 2007. Myzus persicae (green peach aphid) feeding on Arabidopsis induces the formation of a deterrent indole glucosinolate. Plant J. 49:1008–19
    [Google Scholar]
  53. Kim SJ, Lee JS, Kim SM. 2012. 3: 3′-Diindolylmethane suppresses growth of human esophageal squamous cancer cells by G1 cell cycle arrest. Oncol. Rep. 27:1669–73
    [Google Scholar]
  54. Kim YH, Kwon HS, Kim DH, Shin EK, Kang YH et al. 2009. 3,3′-Diindolylmethane attenuates colonic inflammation and tumorigenesis in mice. Inflamm. Bowel Dis. 15:1164–73
    [Google Scholar]
  55. Kong D, Banerjee S, Huang W, Li Y, Wang Z et al. 2008. Mammalian target of rapamycin repression by 3,3′-diindolylmethane inhibits invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC3 cells. Cancer Res. 68:1927–34
    [Google Scholar]
  56. Leader CJ, Clark BJ, Hannah AR, Sammut IA, Wilkins GT, Walker RJ. 2018. Breeding characteristics and dose-dependent blood pressure responses of transgenic Cyp1a1-Ren2 rats. Comp. Med. 68:360–66
    [Google Scholar]
  57. Lee CM, Lee J, Nam MJ, Park SH 2018. Indole-3-carbinol induces apoptosis in human osteosarcoma MG-63 and U2OS cells. Biomed. Res. Int. 2018.7970618
    [Google Scholar]
  58. Lee CM, Park SH, Nam MJ. 2019. Anticarcinogenic effect of indole-3-carbinol (I3C) on human hepatocellular carcinoma SNU449 cells. Hum. Exp. Toxicol. 38:136–47
    [Google Scholar]
  59. Lee J, Yue Y, Park Y, Lee SH. 2017. 3,3′-Diindolylmethane suppresses adipogenesis using AMPKα-dependent mechanism in 3T3-L1 adipocytes and Caenorhabditis elegans. J. Med. Food 20:646–52
    [Google Scholar]
  60. Lee SH, Min KW, Zhang X, Baek SJ. 2013. 3,3′-Diindolylmethane induces activating transcription factor 3 (ATF3) via ATF4 in human colorectal cancer cells. J. Nutr. Biochem. 24:664–71
    [Google Scholar]
  61. Li F, Xu Y, Chen C, Chen SM, Xiao BK, Tao ZZ. 2015. Pro-apoptotic and anti-proliferative effects of 3,3′-diindolylmethane in nasopharyngeal carcinoma cells via downregulation of telomerase activity. Mol. Med. Rep. 12:3815–20
    [Google Scholar]
  62. Li WX, Chen LP, Sun MY, Li JT, Liu HZ, Zhu W. 2015. 3′3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling. Oncotarget 6:23776–92
    [Google Scholar]
  63. Lian JP, Word B, Taylor S, Hammons GJ, Lyn-Cook BD. 2004. Modulation of the constitutive activated STAT3 transcription factor in pancreatic cancer prevention: effects of indole-3-carbinol (I3C) and genistein. Anticancer Res. 24:133–37
    [Google Scholar]
  64. Liang K, Qian WH, Zong J. 2017. 3,3′-Diindolylmethane attenuates cardiomyocyte hypoxia by modulating autophagy in H9c2 cells. Mol. Med. Rep. 16:9553–60
    [Google Scholar]
  65. Lim HM, Park SH, Nam MJ. 2021. Induction of apoptosis in indole-3-carbinol-treated lung cancer H1299 cells via ROS level elevation. Hum. Exp. Toxicol. 40:812–25
    [Google Scholar]
  66. Lin H, Gao X, Chen G, Sun J, Chu J et al. 2015. Indole-3-carbinol as inhibitors of glucocorticoid-induced apoptosis in osteoblastic cells through blocking ROS-mediated Nrf2 pathway. Biochem. Biophys. Res. Commun. 460:422–27
    [Google Scholar]
  67. Ludwig-Müller J, Pieper K, Ruppel M, Cohen JD, Epstein E et al. 1999. Indole glucosinolate and auxin biosynthesis in Arabidopsis thaliana (L.) Heynh. glucosinolate mutants and the development of clubroot disease. Planta 208:409–19
    [Google Scholar]
  68. Marconett CN, Sundar SN, Tseng M, Tin AS, Tran KQ et al. 2011. Indole-3-carbinol downregulation of telomerase gene expression requires the inhibition of estrogen receptor-alpha and Sp1 transcription factor interactions within the hTERT promoter and mediates the G1 cell cycle arrest of human breast cancer cells. Carcinogenesis 32:1315–23
    [Google Scholar]
  69. Megna BW, Carney PR, Nukaya M, Geiger P, Kennedy GD. 2016. Indole-3-carbinol induces tumor cell death: function follows form. J. Surg. Res. 204:47–54
    [Google Scholar]
  70. Meng Q, Qi M, Chen DZ, Yuan R, Goldberg ID 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. 78:155–65
    [Google Scholar]
  71. Mewis I, Khan MA, Glawischnig E, Schreiner M, Ulrichs C. 2012. Water stress and aphid feeding differentially influence metabolite composition in Arabidopsis thaliana (L.). PLOS ONE 7:e48661
    [Google Scholar]
  72. Michnovicz JJ. 1998. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int. J. Obes. Relat. Metab. Disord. 22:227–29
    [Google Scholar]
  73. Mohamad KA, El-Naga RN, Wahdan SA 2022. Neuroprotective effects of indole-3-carbinol on the rotenone rat model of Parkinson's disease: impact of the SIRT1-AMPK signaling pathway. Toxicol. Appl. Pharmacol. 435:115853
    [Google Scholar]
  74. Mohammadi S, Memarian A, Sedighi S, Behnampour N, Yazdani Y. 2018. Immunoregulatory effects of indole-3-carbinol on monocyte-derived macrophages in systemic lupus erythematosus: a crucial role for aryl hydrocarbon receptor. Autoimmunity 51:199–209
    [Google Scholar]
  75. Munakarmi S, Shrestha J, Shin HB, Lee GH, Jeong YJ. 2021. 3,3′-diindolylmethane suppresses the growth of hepatocellular carcinoma by regulating its invasion, migration, and ER stress-mediated mitochondrial apoptosis. Cells 10:51178
    [Google Scholar]
  76. Pedras MS, Nycholat CM, Montaut S, Xu Y, Khan AQ. 2002. Chemical defenses of crucifers: elicitation and metabolism of phytoalexins and indole-3-acetonitrile in brown mustard and turnip. Phytochemistry 59:611–25
    [Google Scholar]
  77. Peng C, Wu C, Xu X, Pan L, Lou Z et al. 2021. Indole-3-carbinol ameliorates necroptosis and inflammation of intestinal epithelial cells in mice with ulcerative colitis by activating aryl hydrocarbon receptor. Exp. Cell Res. 404:112638
    [Google Scholar]
  78. Peters B, Grisk O, Becher B, Wanka H, Kuttler B et al. 2008. Dose-dependent titration of prorenin and blood pressure in Cyp1a1ren-2 transgenic rats: absence of prorenin-induced glomerulosclerosis. J. Hypertens. 26:102–9
    [Google Scholar]
  79. Petersen BL, Chen S, Hansen CH, Olsen CE, Halkier BA. 2002. Composition and content of glucosinolates in developing Arabidopsis thaliana. Planta 214:562–71
    [Google Scholar]
  80. Poornima J, Mirunalini S. 2014. Regulation of carbohydrate metabolism by indole-3-carbinol and its metabolite 3,3′-diindolylmethane in high-fat diet-induced C57BL/6J mice. Mol. Cell. Biochem. 385:7–15
    [Google Scholar]
  81. Prado NJ, Ramirez D, Mazzei L, Parra M, Casarotto M et al. 2022. Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables. Heliyon 8:e08989
    [Google Scholar]
  82. Qian C, Yang C, Lu M, Bao J, Shen H et al. 2021. Activating AhR alleviates cognitive deficits of Alzheimer's disease model mice by upregulating endogenous Aβ catabolic enzyme neprilysin. Theranostics 11:8797–812
    [Google Scholar]
  83. Rajoria S, Suriano R, Wilson YL, Schantz SP, Moscatello A et al. 2011. 3,3′-Diindolylmethane inhibits migration and invasion of human cancer cells through combined suppression of ERK and AKT pathways. Oncol. Rep. 25:491–97
    [Google Scholar]
  84. Rana JS, Khan SS, Lloyd-Jones DM, Sidney S 2021. Changes in mortality in top 10 causes of death from 2011 to 2018. J. Gen. Intern. Med. 36:2517–18
    [Google Scholar]
  85. Riby JE, Firestone GL, Bjeldanes LF. 2008. 3,3′-diindolylmethane reduces levels of HIF-1α and HIF-1 activity in hypoxic cultured human cancer cells. Biochem. Pharmacol. 75:1858–67
    [Google Scholar]
  86. Rungapamestry V, Duncan AJ, Fuller Z, Ratcliffe B. 2006. Changes in glucosinolate concentrations, myrosinase activity, and production of metabolites of glucosinolates in cabbage (Brassica oleracea var. capitata) cooked for different durations. J. Agric. Food Chem. 54:7628–34
    [Google Scholar]
  87. Saini N, Akhtar A, Chauhan M, Dhingra N, Pilkhwal Sah S 2020. Protective effect of indole-3-carbinol, an NF-κB inhibitor in experimental paradigm of Parkinson's disease: in silico and in vivo studies. Brain Behav. Immun. 90:108–37
    [Google Scholar]
  88. Sarkar FH, Rahman KM, Li Y. 2003. Bax translocation to mitochondria is an important event in inducing apoptotic cell death by indole-3-carbinol (I3C) treatment of breast cancer cells. J. Nutr. 133:2434S–39S
    [Google Scholar]
  89. Siegel RL, Miller KD, Fuchs HE, Jemal A. 2021. Cancer statistics, 2021. CA Cancer J. Clin. 71:7–33
    [Google Scholar]
  90. Song L, Thornalley PJ. 2007. Effect of storage, processing and cooking on glucosinolate content of Brassica vegetables. Food Chem. Toxicol. 45:216–24
    [Google Scholar]
  91. Tian X, Liu K, Zu X, Ma F, Li Z et al. 2019. 3,3′-Diindolylmethane inhibits patient-derived xenograft colon tumor growth by targeting COX1/2 and ERK1/2. Cancer Lett. 448:20–30
    [Google Scholar]
  92. Tsai JT, Liu HC, Chen YH. 2010. Suppression of inflammatory mediators by cruciferous vegetable-derived indole-3-carbinol and phenylethyl isothiocyanate in lipopolysaccharide-activated macrophages. Mediat. Inflamm. 2010.293642
    [Google Scholar]
  93. Vallejo F, Tomás-Barberán F, García-Viguera C. 2002. Glucosinolates and vitamin C content in edible parts of broccoli florets after domestic cooking. Eur. Food Res. Technol. 215:310–16
    [Google Scholar]
  94. Velasco P, Cartea ME, Gonzalez C, Vilar M, Ordas A. 2007. Factors affecting the glucosinolate content of kale (Brassica oleracea acephala group). J. Agric. Food Chem. 55:955–62
    [Google Scholar]
  95. Verkerk R, Dekker M, Jongen WM. 2001. Post-harvest increase of indolyl glucosinolates in response to chopping and storage of Brassica vegetables. J. Sci. Food Agric. 81:953–58
    [Google Scholar]
  96. Wang ML, Lin SH, Hou YY, Chen YH. 2016. Suppression of lipid accumulation by indole-3-carbinol is associated with increased expression of the aryl hydrocarbon receptor and CYP1B1 proteins in adipocytes and with decreased adipocyte-stimulated endothelial tube formation. Int. J. Mol. Sci. 17:81256
    [Google Scholar]
  97. Wang ML, Shih CK, Chang HP, Chen YH. 2012. Antiangiogenic activity of indole-3-carbinol in endothelial cells stimulated with activated macrophages. Food Chem. 134:811–20
    [Google Scholar]
  98. Wang X, Zhao Y, Yu M, Xu Y 2020. PTEN/Akt signaling-mediated activation of the mitochondrial pathway contributes to the 3,3′-diindolylmethane-mediated antitumor effect in malignant melanoma cells. J. Med. Food 23:1248–58
    [Google Scholar]
  99. Wang YQ, Chen C, Chen Z, Xu Y, Wang Y et al. 2013. Indole-3-carbinol inhibits cell proliferation and induces apoptosis in Hep-2 laryngeal cancer cells. Oncol. Rep. 30:227–33
    [Google Scholar]
  100. Williams DE. 2021. Indoles derived from glucobrassicin: cancer chemoprevention by indole-3-carbinol and 3,3′-diindolylmethane. Front. Nutr. 8:734334
    [Google Scholar]
  101. Williams DJ, Critchley C, Pun S, Chaliha M, O'Hare TJ. 2010. Key role of Fe2+ in epithiospecifier protein activity. J. Agric. Food Chem. 58:8512–21
    [Google Scholar]
  102. Windsor AJ, Reichelt M, Figuth A, Svatos A, Kroymann J et al. 2005. Geographic and evolutionary diversification of glucosinolates among near relatives of Arabidopsis thaliana (Brassicaceae). Phytochemistry 66:1321–33
    [Google Scholar]
  103. Wittstock U, Halkier BA. 2002. Glucosinolate research in the Arabidopsis era. Trends Plant Sci. 7:263–70
    [Google Scholar]
  104. Wu TY, Saw CL, Khor TO, Pung D, Boyanapalli SS, Kong AN. 2012. In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: involvement of Nrf2 and cell cycle/apoptosis signaling pathways. Mol. Carcinog. 51:761–70
    [Google Scholar]
  105. Wu Y, Wang J, He Q, Yu L, Pham Q et al. 2020. Dietary indole-3-carbinol alleviated spleen enlargement, enhanced IgG response in C3H/HeN mice infected with Citrobacter rodentium. Nutrients 12:103148
    [Google Scholar]
  106. Xu Y, Zhang J, Shi W, Liu Y. 2013. Anticancer effects of 3,3′-diindolylmethane are associated with G1 arrest and mitochondria-dependent apoptosis in human nasopharyngeal carcinoma cells. Oncol. Lett. 5:655–62
    [Google Scholar]
  107. Yang H, Seo SG, Shin SH, Min S, Kang MJ et al. 2017. 3,3′-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Mol. Nutr. Food Res. 61:101700119
    [Google Scholar]
  108. Yu TY, Pang WJ, Yang GS. 2015. 3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice. J. Pharmacol. Sci. 127:75–82
    [Google Scholar]
  109. Yuan GF, Sun B, Yuan J, Wang QM. 2009. Effects of different cooking methods on health-promoting compounds of broccoli. J. Zhejiang Univ. Sci. B 10:580–88
    [Google Scholar]
  110. Zhang Z, Ober JA, Kliebenstein DJ. 2006. The gene controlling the quantitative trait locus EPITHIOSPECIFIER MODIFIER1 alters glucosinolate hydrolysis and insect resistance in Arabidopsis. Plant Cell 18:1524–36
    [Google Scholar]
  111. Zhu P, Yu H, Zhou K, Bai Y, Qi R, Zhang S. 2020. 3,3′-Diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to reverse epithelial-mesenchymal transition through repressing RhoA/ROCK1-mediated COX2/PGE2 pathway. J. Exp. Clin. Cancer Res. 39:113
    [Google Scholar]
/content/journals/10.1146/annurev-food-060721-025531
Loading
/content/journals/10.1146/annurev-food-060721-025531
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error