Micronutrients and Supplements Info: Indole-3-Carbinol

Indole-3-Carbinol

Description

Indole-3-Carbinol is a product of the hydrolysis of glucobrassicin, a compound specifically found in cruciferous vegetables (Brassicaceae family).

Function

Some studies tend to show that Indole-3-Carbinol may have anti-cancer properties. It is also investigated for its potential beneficial effect against diseases related to the Human Papilloma Virus (HPV), such as Cervical Intraepithelial Neoplasia and Recurrent Respiratory Papillomatosis.

Sources

Glucobrassicin is found in many cruciferous vegetables, especially broccoli, Brussels sprouts, cabbage, cauliflower, collard greens, kale, kohlrabi, mustard greens, radish, rutabaga, and turnip.

Toxicity

Neurological symptoms such as disequilibrium and tremor have been described with high doses but symptoms subsided when the dose was reduced. The safety of Indole-3-Carbinol supplements during pregnancy and lactation has not been studied. In addition, it may interfere with a liver enzyme involved in the metabolism of many other therapeutic drugs. There is therefore a potential risk for adverse drug interactions, and caution should be used when Indole-3-Carbinol is taken with other drugs.

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Additional Sources of Information:

Indole-3-Carbinol - Wikipedia

Indole-3-Carbinol - Linus Pauling Institute

Scientific References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Beneficial and adverse effects of chemopreventive agents. Lee BM, Park KK. Mutat Res. 2003;523-524:265-278.

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

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

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

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

Chapter 17: Genital human papillomavirus infections--current and prospective therapies. Stanley M. J Natl Cancer Inst Monogr. 2003(31):117-124.

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

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

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

Development of a food composition database for the estimation of dietary intakes of glucosinolates, the biologically active constituents of cruciferous vegetables. McNaughton SA, Marks GC. Br J Nutr. 2003;90(3):687-697.

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

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. Yoshida M, Katashima S, Ando J, et al. Carcinogenesis. 2004;25(11):2257-2264.

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

Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Conaway CC, Getahun SM, Liebes LL, et al. Nutr Cancer. 2000;38(2):168-178.

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

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

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. Morse MA, LaGreca SD, Amin SG, Chung FL. Cancer Res. 1990;50(9):2613-2617.

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

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

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

Estrogen metabolism and laryngeal papillomatosis: a pilot study on dietary prevention. Auborn K, Abramson A, Bradlow HL, Sepkovic D, Mullooly V. Anticancer Res. 1998;18(6B):4569-4573.

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

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

Glucosinolates and their breakdown products in food and food plants. Fenwick GR, Heaney RK, Mullin WJ. Crit Rev Food Sci Nutr. 1983;18(2):123-201.

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

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

Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Rouzaud G, Young SA, Duncan AJ. Cancer Epidemiol Biomarkers Prev. 2004;13(1):125-131.

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

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

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. He YH, Friesen MD, Ruch RJ, Schut HA. Food Chem Toxicol. 2000;38(1):15-23.

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

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

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

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. Howells LM, Gallacher-Horley B, Houghton CE, Manson MM, Hudson EA. Mol Cancer Ther. 2002;1(13):1161-1172.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Pilot study: effect of 3,3'-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Nutr Cancer. 2004;50(2):161-167.

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

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

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

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

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. Dashwood RH, Fong AT, Williams DE, Hendricks JD, Bailey GS. Cancer Res. 1991;51(9):2362-2365.

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. Guo D, Schut HA, Davis CD, Snyderwine EG, Bailey GS, Dashwood RH. Carcinogenesis. 1995;16(12):2931-2937.

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

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

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

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

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

Therapy for recurrent respiratory papillomatosis. Auborn KJ. Antivir Ther. 2002;7(1):1-9.

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

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

Variation of glucosinolates in vegetable crops of Brassica oleracea. Kushad MM, Brown AF, Kurilich AC, et al. J Agric Food Chem. 1999;47(4):1541-1548.

Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential. Hording U, Junge J, Poulsen H, Lundvall F. Gynecol Oncol. 1995;56(2):276-279.

What is recurrent respiratory papillomatosis? Recurrent Respiratory Papillomatosis Foundation.