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References: Indole-3-Carbinol


1.  Verhoeven DT, Verhagen H, Goldbohm RA, van den Brandt PA, van Poppel G. A review of mechanisms underlying anticarcinogenicity by brassica vegetables. Chem Biol Interact. 1997;103(2):79-129.  (PubMed)

2.  Kim YS, Milner JA. Targets for indole-3-carbinol in cancer prevention. J Nutr Biochem. 2005;16(2):65-73.  (PubMed)

3.  Holst B, Williamson G. A critical review of the bioavailability of glucosinolates and related compounds. Nat Prod Rep. 2004;21(3):425-447.  (PubMed)

4.  Shertzer HG, Senft AP. The micronutrient indole-3-carbinol: implications for disease and chemoprevention. Drug Metabol Drug Interact. 2000;17(1-4):159-188.  (PubMed)

5.  Bjeldanes LF, Kim JY, Grose KR, Bartholomew JC, Bradfield CA. Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci U S A. 1991;88(21):9543-9547.  (PubMed)

6.  Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables. Cancer Epidemiol Biomarkers Prev. 1998;7(12):1091-1100.  (PubMed)

7.  Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr. 2002;132(10):2991-2994.  (PubMed)

8.  Bonnesen C, Eggleston IM, Hayes JD. 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. 2001;61(16):6120-6130.  (PubMed)

9.  Safe S. Molecular biology of the Ah receptor and its role in carcinogenesis. Toxicol Lett. 2001;120(1-3):1-7.  (PubMed)

10.  Nho CW, Jeffery E. The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous vegetables. Toxicol Appl Pharmacol. 2001;174(2):146-152.  (PubMed)

11.  Wallig MA, Kingston S, Staack R, Jefferey EH. Induction of rat pancreatic glutathione S-transferase and quinone reductase activities by a mixture of glucosinolate breakdown derivatives found in Brussels sprouts. Food Chem Toxicol. 1998;36(5):365-373.  (PubMed)

12.  Baird WM, Hooven LA, Mahadevan B. Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen. 2005;45(2-3):106-114.  (PubMed)

13.  Jordan VC, Gapstur S, Morrow M. Selective estrogen receptor modulation and reduction in risk of breast cancer, osteoporosis, and coronary heart disease. J Natl Cancer Inst. 2001;93(19):1449-1457.  (PubMed)

14.  Liehr JG. Is estradiol a genotoxic mutagenic carcinogen? Endocr Rev. 2000;21(1):40-54.  (PubMed)

15.  Ashok BT, Chen Y, Liu X, Bradlow HL, Mittelman A, Tiwari RK. Abrogation of estrogen-mediated cellular and biochemical effects by indole-3-carbinol. Nutr Cancer. 2001;41(1-2):180-187.  (PubMed)

16.  Meng Q, Yuan F, Goldberg ID, Rosen EM, Auborn K, Fan S. Indole-3-carbinol is a negative regulator of estrogen receptor-alpha signaling in human tumor cells. J Nutr. 2000;130(12):2927-2931.  (PubMed)

17.  Chen I, McDougal A, Wang F, Safe S. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis. 1998;19(9):1631-1639.  (PubMed)

18.  Leong H, Riby JE, Firestone GL, Bjeldanes LF. 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. 2004;18(2):291-302.  (PubMed)

19.  Riby JE, Feng C, Chang YC, Schaldach CM, Firestone GL, Bjeldanes LF. The major cyclic trimeric product of indole-3-carbinol is a strong agonist of the estrogen receptor signaling pathway. Biochemistry. 2000;39(5):910-918.  (PubMed)

20.  Shilling AD, Carlson DB, Katchamart S, Williams DE. 3,3'-Diindolylmethane, a major condensation product of indole-3-carbinol, is a potent estrogen in the rainbow trout. Toxicol Appl Pharmacol. 2001;170(3):191-200.  (PubMed)

21.  Telang NT, Suto A, Wong GY, Osborne MP, Bradlow HL. Induction by estrogen metabolite 16 alpha-hydroxyestrone of genotoxic damage and aberrant proliferation in mouse mammary epithelial cells. J Natl Cancer Inst. 1992;84(8):634-638.  (PubMed)

22.  Yuan F, Chen DZ, Liu K, Sepkovic DW, Bradlow HL, Auborn K. Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer. Anticancer Res. 1999;19(3A):1673-1680.  (PubMed)

23.  Bradlow HL, Telang NT, Sepkovic DW, Osborne MP. 2-Hydroxyestrone: the 'good' estrogen. J Endocrinol. 1996;150 Suppl:S259-265.  (PubMed)

24.  McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuite M. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus. 2001;10(11):779-783.  (PubMed)

25.  Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev. 1994;3(7):591-595.  (PubMed)

26.  Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab Disord. 1998;22(3):227-229.  (PubMed)

27.  Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997;89(10):718-723.  (PubMed)

28.  Wong GY, Bradlow L, Sepkovic D, Mehl S, Mailman J, Osborne MP. Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl. 1997;28-29:111-116.  (PubMed)

29.  Reed GA, Peterson KS, Smith HJ, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005;14(8):1953-1960.  (PubMed)

30.  Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. 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. 2004;50(2):161-167.  (PubMed)

31.  Ho GH, Luo XW, Ji CY, Foo SC, Ng EH. Urinary 2/16 alpha-hydroxyestrone ratio: correlation with serum insulin-like growth factor binding protein-3 and a potential biomarker of breast cancer risk. Ann Acad Med Singapore. 1998;27(2):294-299.  (PubMed)

32.  Kabat GC, Chang CJ, Sparano JA, et al. Urinary estrogen metabolites and breast cancer: a case-control study. Cancer Epidemiol Biomarkers Prev. 1997;6(7):505-509.  (PubMed)

33.  Schneider J, Kinne D, Fracchia A, et al. Abnormal oxidative metabolism of estradiol in women with breast cancer. Proc Natl Acad Sci U S A. 1982;79(9):3047-3051.  (PubMed)

34.  Cauley JA, Zmuda JM, Danielson ME, et al. Estrogen metabolites and the risk of breast cancer in older women. Epidemiology. 2003;14(6):740-744.  (PubMed)

35.  Meilahn EN, De Stavola B, Allen DS, et al. Do urinary oestrogen metabolites predict breast cancer? Guernsey III cohort follow-up. Br J Cancer. 1998;78(9):1250-1255.  (PubMed)

36.  Ursin G, London S, Stanczyk FZ, et al. Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 1999;91(12):1067-1072.  (PubMed)

37.  Stewart ZA, Westfall MD, Pietenpol JA. Cell-cycle dysregulation and anticancer therapy. Trends Pharmacol Sci. 2003;24(3):139-145.  (PubMed)

38.  Chinni SR, Li Y, Upadhyay S, Koppolu PK, Sarkar FH. Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene. 2001;20(23):2927-2936.  (PubMed)

39.  Cover CM, Hsieh SJ, Tran SH, et al. 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. 1998;273(7):3838-3847.  (PubMed)

40.  Stresser DM, Williams DE, Griffin DA, Bailey GS. Mechanisms of tumor modulation by indole-3-carbinol. Disposition and excretion in male Fischer 344 rats. Drug Metab Dispos. 1995;23(9):965-975.  (PubMed)

41.  Hong C, Firestone GL, Bjeldanes LF. Bcl-2 family-mediated apoptotic effects of 3,3'-diindolylmethane (DIM) in human breast cancer cells. Biochem Pharmacol. 2002;63(6):1085-1097.  (PubMed)

42.  Howells LM, Gallacher-Horley B, Houghton CE, Manson MM, Hudson EA. Indole-3-carbinol inhibits protein kinase B/Akt and induces apoptosis in the human breast tumor cell line MDA MB468 but not in the nontumorigenic HBL100 line. Mol Cancer Ther. 2002;1(13):1161-1172.  (PubMed)

43.  Rahman KW, Sarkar FH. Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3'-diindolylmethane-induced apoptosis in breast cancer cells. Cancer Res. 2005;65(1):364-371.  (PubMed)

44.  Abdelrahim M, Newman K, Vanderlaag K, Samudio I, Safe S. 3,3'-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis. 2006;27(4):717-728.  (PubMed)

45.  Chen D, Carter TH, Auborn KJ. Apoptosis in cervical cancer cells: implications for adjunct anti-estrogen therapy for cervical cancer. Anticancer Res. 2004;24(5A):2649-2656.  (PubMed)

46.  Meng Q, Goldberg ID, Rosen EM, Fan S. Inhibitory effects of Indole-3-carbinol on invasion and migration in human breast cancer cells. Breast Cancer Res Treat. 2000;63(2):147-152.  (PubMed)

47.  Chang X, Tou JC, Hong C, et al. 3,3'-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis. 2005;26(4):771-778.  (PubMed)

48.  Wu HT, Lin SH, Chen YH. Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables. J Agric Food Chem. 2005;53(13):5164-5169.  (PubMed)

49.  Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev. 1996;5(9):733-748.  (PubMed)

50.  Fahey JW, Zalcmann AT, Talalay P. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry. 2001;56(1):5-51.  (PubMed)

51.  Grubbs CJ, Steele VE, Casebolt T, et al. Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol. Anticancer Res. 1995;15(3):709-716.  (PubMed)

52.  Bradlow HL, Michnovicz J, Telang NT, Osborne MP. Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis. 1991;12(9):1571-1574.  (PubMed)

53.  Kojima T, Tanaka T, Mori H. Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res. 1994;54(6):1446-1449.  (PubMed)

54.  Wattenberg LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res. 1978;38(5):1410-1413.  (PubMed)

55.  Wargovich MJ, Chen CD, Jimenez A, et al. Aberrant crypts as a biomarker for colon cancer: evaluation of potential chemopreventive agents in the rat. Cancer Epidemiol Biomarkers Prev. 1996;5(5):355-360.  (PubMed)

56.  Guo D, Schut HA, Davis CD, Snyderwine EG, Bailey GS, Dashwood RH. Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat. Carcinogenesis. 1995;16(12):2931-2937.  (PubMed)

57.  Morse MA, LaGreca SD, Amin SG, Chung FL. Effects of indole-3-carbinol on lung tumorigenesis and DNA methylation induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and on the metabolism and disposition of NNK in A/J mice. Cancer Res. 1990;50(9):2613-2617.  (PubMed)

58.  Dashwood RH, Arbogast DN, Fong AT, Hendricks JD, Bailey GS. Mechanisms of anti-carcinogenesis by indole-3-carbinol: detailed in vivo DNA binding dose-response studies after dietary administration with aflatoxin B1. Carcinogenesis. 1988;9(3):427-432.  (PubMed)

59.  Oganesian A, Hendricks JD, Williams DE. Long term dietary indole-3-carbinol inhibits diethylnitrosamine-initiated hepatocarcinogenesis in the infant mouse model. Cancer Lett. 1997;118(1):87-94.  (PubMed)

60.  Dashwood RH, Fong AT, Williams DE, Hendricks JD, Bailey GS. Promotion of aflatoxin B1 carcinogenesis by the natural tumor modulator indole-3-carbinol: influence of dose, duration, and intermittent exposure on indole-3-carbinol promotional potency. Cancer Res. 1991;51(9):2362-2365.  (PubMed)

61.  Oganesian A, Hendricks JD, Pereira CB, Orner GA, Bailey GS, Williams DE. Potency of dietary indole-3-carbinol as a promoter of aflatoxin B1-initiated hepatocarcinogenesis: results from a 9000 animal tumor study. Carcinogenesis. 1999;20(3):453-458.  (PubMed)

62.  Stoner G, Casto B, Ralston S, Roebuck B, Pereira C, Bailey G. Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol. Carcinogenesis. 2002;23(2):265-272.  (PubMed)

63.  Kim DJ, Lee KK, Han BS, Ahn B, Bae JH, Jang JJ. Biphasic modifying effect of indole-3-carbinol on diethylnitrosamine-induced preneoplastic glutathione S-transferase placental form-positive liver cell foci in Sprague-Dawley rats. Jpn J Cancer Res. 1994;85(6):578-583.  (PubMed)

64.  Kim DJ, Han BS, Ahn B, et al. Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model. Carcinogenesis. 1997;18(2):377-381.  (PubMed)

65.  Pence BC, Buddingh F, Yang SP. Multiple dietary factors in the enhancement of dimethylhydrazine carcinogenesis: main effect of indole-3-carbinol. J Natl Cancer Inst. 1986;77(1):269-276.  (PubMed)

66.  Suzui M, Inamine M, Kaneshiro T, et al. Indole-3-carbinol inhibits the growth of human colon carcinoma cells but enhances the tumor multiplicity and volume of azoxymethane-induced rat colon carcinogenesis. Int J Oncol. 2005;27(5):1391-1399.  (PubMed)

67.  Yoshida M, Katashima S, Ando J, et al. Dietary indole-3-carbinol promotes endometrial adenocarcinoma development in rats initiated with N-ethyl-N'-nitro-N-nitrosoguanidine, with induction of cytochrome P450s in the liver and consequent modulation of estrogen metabolism. Carcinogenesis. 2004;25(11):2257-2264.  (PubMed)

68.  Yu Z, Mahadevan B, Lohr CV, et al. Indole-3-carbinol in the maternal diet provides chemoprotection for the fetus against transplacental carcinogenesis by the polycyclic aromatic hydrocarbon dibenzo[a,l]pyrene. Carcinogenesis. 2006;27(10):2116-2123.  (PubMed)

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70.  Dashwood RH. Indole-3-carbinol: anticarcinogen or tumor promoter in brassica vegetables? Chem Biol Interact. 1998;110(1-2):1-5.  (PubMed)

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72.  Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr. 2003(31):3-13.  (PubMed)

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

74.  Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000;78(2):123-129.  (PubMed)

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77.  Naik R, Nixon S, Lopes A, Godfrey K, Hatem MH, Monaghan JM. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer. 2006;16(2):786-790.  (PubMed)

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80.  Newfield L, Goldsmith A, Bradlow HL, Auborn K. Estrogen metabolism and human papillomavirus-induced tumors of the larynx: chemo-prophylaxis with indole-3-carbinol. Anticancer Res. 1993;13(2):337-341.  (PubMed)

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82.  Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998;118(6):810-815.  (PubMed)

83.  Rosen CA, Bryson PC. Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J Voice. 2004;18(2):248-253.  (PubMed)

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86.  Auborn KJ, Qi M, Yan XJ, et al. Lifespan is prolonged in autoimmune-prone (NZB/NZW) F1 mice fed a diet supplemented with indole-3-carbinol. J Nutr. 2003;133(11):3610-3613.  (PubMed)

87.  Carlson DG, Kwolek WF, Williams PH. Glucosinolates in crucifer vegetables: broccoli, Brussels sprouts, cauliflower, collards, kale, mustard greens, and kohlrabi. J Amer Soc Hort Sci. 1987;112(1):173-178.

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91.  Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev. 2001;10(5):501-508.  (PubMed)

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94.  Verkerk R, Dekker M. Glucosinolates and myrosinase activity in red cabbage (Brassica oleracea L. var. Capitata f. rubra DC.) after various microwave treatments. J Agric Food Chem. 2004;52(24):7318-7323.  (PubMed)

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96.  He YH, Friesen MD, Ruch RJ, Schut HA. Indole-3-carbinol as a chemopreventive agent in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) carcinogenesis: inhibition of PhIP-DNA adduct formation, acceleration of PhIP metabolism, and induction of cytochrome P450 in female F344 rats. Food Chem Toxicol. 2000;38(1):15-23.  (PubMed)

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98.  Leibelt DA, Hedstrom OR, Fischer KA, Pereira CB, Williams DE. Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in sprague-dawley rats. Toxicol Sci. 2003;74(1):10-21.  (PubMed)