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Home > Antiaging Research > Indole-3-Carbinol

Indole-3-Carbinol (I3C)

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News & Research:

  • How dietary supplement may block cancer cells - Science Daily, 6/29/10 - "The research showed that I3C causes the destruction of that molecule and thereby blocks the growth of breast cancer cells ... Cdc25A is present at abnormally high levels in about half of breast cancer cases, and it is associated with a poor prognosis ... The molecule also occurs at abnormally high levels in cancers of the breast, prostate, liver, esophagus, endometrium and colon, and in non-Hodgkin lymphoma, and in other diseases such as Alzheimer's disease ... I3C can have striking effects on cancer cells ... When the substance was given orally to the mice, it reduced tumor size by up to 65 percent. They also showed that I3C had no affect on breast-cell tumors in which the Cdc25A molecule had a mutation in that key location"
  • Indole-3: A Broccoli Cure? - Dr. Weil, 9/15/06
  • Broccoli Compound Targets Key Enzyme In Late-stage Cancer - Science Daily, 12/14/08 - "The new findings are the first to explain how indole-3-carbinol (I3C) stops cell growth, and thus provides the basis for designing improved versions of the chemical that would be more effective as a drug and could work against a broader range of breast as well as prostate tumors ... I3C inhibits the enzyme elastase, which at high levels in breast cancer cells heralds a poor prognosis: decreased response to chemotherapy, reduced response to endocrine treatment and reduced survival rates" - See indole-3-carbinol at Amazon.com.
  • Broccoli compound may inhibit lung cancer from tobacco smoke: Study - Nutra USA, 12/8/08 - "exposed experimental mice to carcinogenic compounds found in tobacco smoke called 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo(a)pyrene (BaP) ... This resulted in an average of 21 tumours per mouse after 16 weeks. However, mice fed diets containing 1, 10, 30, 71, and 112 micromoles per gram of I3C were found to have reductions in the number of tumours by 15, 51, 53, 75, and 88 per cent, respectively"
  • Broccoli compound identified for heart benefits - Nutra USA, 10/3/07 - "the indole-based compound, indole-3-carbinol, was able to reduce the secretion of apolipoprotein B-100 (apoB) by 56 per cent, and thereby confer cardiovascular benefits"
  • Broccoli chemical's cancer check - BBC News, 2/7/06 - "A chemical in vegetables such as broccoli, cauliflower and cabbage can boost DNA repair in cells and may stop them becoming cancerous ... Vegetables such as broccoli were found to contain a compound called I3C"
  • I3C & DIM - Natural, Dual-Action Protection Against Deadly Cancers - Life Extension Magazine, 1/06 - "Mounting preclinical and clinical evidence indicate[s] that indole-3-carbinol (I3C), a key bio-active food component in cruciferous vegetables, has multiple anticarcinogenic and antitumorigenic properties"
  • Ward off cancer with a Japanese diet - MSNBC, 12/17/04 - "Cruciferous vegetables make a unique contribution to good health. They contain natural substances called glucosinolates that break down in the body to form indoles and other compounds that fight cancer development in several different ways"
  • I3C May Reverse Autoimmunity and Extend Life Span - Life Extension Magazine, 9/04 - "So the question remains: by ameliorating autoimmunity, could I3C increase longevity in humans? Time will tell. Meanwhile, consider that rodents who took their I3C supplements were scurrying around in a laboratory in New York at the equivalent of 120 human years"
  • Can Broccoli Prevent Lupus? - WebMD, 11/6/03 - "I3C is believed to act as an anti-estrogen ... At 12 months of age, 80% of the mice fed the I3C diet from soon after birth were alive, compared with only 10% of the non-supplemented mice. Normal mice live from one to two years ... I3C-fed mice had far fewer kidney problems than the mice whose diets were not supplemented, and researchers say this is the reason that they lived much longer. Kidney disease is one of the main, life-threatening complications of lupus" - See indole-3-carbinol at Amazon.com.
  • A Broccoli Cure? - Dr. Weil, 10/23/02
  • Prostate Cancer and I3C - Life Extension Magazine, 5/02 - "Studies show that I3C changes not only estrogen metabolism, but testosterone and androsterone as well. Its hormone-altering action may help protect against hormone mimickers such as the drugs implanted in food animals. It has been confirmed that whether a hormone is the real thing, a drug facsimilie or a chemical, I3C will neutralize it"
  • Does Vitamin E Prevent Breast Cancer? - Life Extension Magazine, 5/02 - "premenopausal women with a family history who consumed the highest quantity of vitamin E enjoyed a 43% reduction in breast cancer incidence compared to only a 16% risk reduction for women without a family history of breast cancer.[11] Based on this study, vitamin E appears to protect against genetic- predisposed breast cancer better than environmental-induced breast cancer. (Note that nutrients like indole-3-carbinol may specifically protect against environmental breast carcinogens.)"
  • I have read that Indole-3-Carbinol (I3C) actually increases the activity of aromatase enzyme and that DIM does not - Life Extension Magazine, 3/01 - "In one study, men received I3C for one week; a profile of 13 estrogens was measured. The results were that I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol and 16 alpha-hydroxyestrone, were lower after I3C treatment [J Natl Cancer Inst 1997 May 21;89(10):718-23]. On the other hand, studies have shown that DIM can actually induce aromatase activity with a two-fold increase [Toxicol Sci 2001 May;61(1):40-8]" - The following are the two references for that statement:
    • 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Diindolylmethanes Differentially Induce Cytochrome P450 1A1, 1B1, and 19 in H295R Human Adrenocortical Carcinoma Cells - Toxicol Sci 2001 May;61(1):40-8 - "DIM, but not TCDD, induced aromatase activity with an apparently maximal 2-fold increase at 10 µM; higher concentrations of DIM and many of its analogs were cytotoxic"
    • Changes in levels of urinary estrogen metabolites after oral indole-3- carbinol treatment in humans - J Natl Cancer Inst 1997 May 21;89(10):718-23 - "In both men and women, I3C significantly increased the urinary excretion of C-2 estrogens. The urinary concentrations of nearly all other estrogen metabolites, including levels of estradiol, estrone, estriol, and 16alpha- hydroxyestrone, were lower after I3C treatment" - So if C-2 estrogens are increased, is that bad in men?  I don't know. The following are all I could find:
      • Estrogen Metabolism - immunacare.com - "C-2 metabolites are essentially devoid of peripheral biological activity, as shown in studies on uterine weight, gonadotrophin secretion, and cell proliferation {1}. 2-Hydroxyestrogen has even been found to exert a modest anti-estrogenic effect {2,3}, and has been called "the good estrogen" {4}. The 16a-hydroxylated metabolites, 16a-hydroxyestrone (16OHE1) and estriol (E3), are estrogen agonists {5}."
      • Effects of Pesticides on the Ratio of 16/2-Hydroxyestrone: A Biologic Marker of Breast Cancer Risk - Environmental Health Perspectives 103, Supplement 7, October 1995 -"Estradiol metabolism proceeds by hydroxylation at one of two mutually exclusive sites at C-2 and C-16. The catechol pathway yields the weakly estrogenic 2-hydroxyestrone (2-OHE1), which inhibits breast cell proliferation" - If that means, and I think it does, that the C-2 metabolites inhibit breast cell growth, that would definitely be a good thing for men.
      • Breast-Cancer Risk - Pondicherry.com, 6/00 - "Earlier research has shown that hydroxylation at the C-2 position produces metabolites with little or no estrogenic activity and thus might be associated with decreased breast-cancer risk ... Women with predominately C-2 pathway by-products (those with low activity) were 40 percent less likely to have developed breast cancer during those five years"
  • I3C vs DIM - Life Extension Foundation, 1/02
  • Mutated Hormones That Cause Cancer - Life Extension Foundation, 12/01 - "The question arises, then, that if I3C and other compounds can change the way our body's own estrogen behaves, could it do the same to estrogen-mimicking chemicals? What about chemical estrogens? Could I3C help us detoxify the estrogen-like chemicals in our milk jugs and plastic wrap? The answer is probably. While definitive proof is not available yet, preliminary studies indicate that I3C can detoxify fake estrogens the same way it does real estrogens"
  • I3C as possible treatment for ovarian cancer - Life Extension Foundation, 6/01
  • New findings on I3C - Life Extension Magazine, 5/01 - "These findings are the latest in a growing list of what I3C does to modulate estrogen. One of its most important actions is to change the way estrogen is metabolized. Instead of transforming into 16-a-hydroxyestrone, estrogen is converted to 2-hydroxyestrone when I3C is present. 2-hydroxyestrone is a weaker form of estrogen. Women with more 2-hydroxyestrone than 16-a-hydroxyestrone are at less risk for breast cancer than those with higher levels of the 16 metabolite. Another feat of I3C is to block carcinogens from causing cancer. In addition, I3C can prevent cervical cancer caused by human papilloma virus-16 in mice. I3C also causes apoptosis (cell death) in certain types of cancer cells"
  • Long-term estrogen use doubles cancer risk - USA Today, 3/20/01 - "Women who used estrogen replacement therapy for at least 10 years were twice as likely to die of ovarian cancer than women who never used it"
  • Prostate Cancer and Cruciferous Vegetables - Life Extension Magazine, 7/00
  • I3C Indole 3 carbinol The Tamoxifen Substitute - Life Extension Foundation, 10/99
  • Estrogen Levels Linked To Head And Neck Cancers - Doctor's Guide, 9/28/99 - "Similar effects (to alter estrogen metabolic pathways) could be exerted by vegetables including broccoli and cauliflower, which contain the phytochemical compound indole-3-carbinol."
  • Reducing the Hormone Related Cancer Risk (Or cabbages, sex hormones and their metabolites) - Jonathan Wright M.D., International Anti-aging Systems - "Among other things, estradiol is metabolized into estrone, which in turn can be metabolized into either 2-hydroxyestrone or 16 alpha-hydroxyestrone. Importantly, there's an “inverse” relationship here: if more 2-hydroxyestrone is made, less 16 alpha-hydroxyestrone is usually made, and vice-versa. In at least one of his publications, Dr. Bradlow has termed 2-hydroxyestrone “good estrogen”, and has given us evidence that 16 alpha hydroxyestrone is “bad estrogen”. He writes: “Evidence from a long series of studies has demonstrated a specific role for 16a-hydroxyestrone as a transforming estrogen, which is more potent than estradiol itself.” (“Transforming” refers to the tendency of 16a-hydroxyestrone to increase cellular growth and proliferation, and even cancerous transformation in estrogen-responsive tissues). He goes on to note that the preponderance of evidence shows that, by contrast, 2-hydroxyestrone is non-carcinogenic or even anti-carcinogenic. He also notes that treatment which reduces the 2/16a hydroxyestrone ratio has been shown to reverse the growth of human larygneal papillomas, caused by the same family of viruses (HPV) implicated in cervical cancers.  Other researchers hypothesize that cancer in other tissues, including uterus, prostate, liver and kidney, may be affected by the 2/16a hydroxyestrone ratio as well as other estrogen metabolites"
  • I3C/DIM - Recurrent Respiratory Papillomatosis Foundation

Abstracts:

  • Indole-3-carbinol protects against pressure overload induced cardiac remodeling via activating AMPK-α - Mol Nutr Food Res. 2013 Apr 27 - "Indole-3-carbinol (I3C), a monomer component extracted from leaves and stems of cruciferous vegetables, has inhibitory effects on tumors, obesity, and liver fibrosis ... We determined the effects of I3C on cardiac remodeling and heart function using an aortic banding (AB) mouse model ... I3C both prevents and reverses cardiac remodeling by activating AMPK-α signaling. I3C is a potential therapeutic drug for heart failure"
  • 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. 2008 Dec 15 - "Using chemotaxis and fluorescent-bead cell motility assays, we demonstrated that I3C significantly decreased the in vitro migration of MDA-MB-231 cells, a highly invasive breast cancer cell line" - See indole-3-carbinol at Amazon.com.
  • Indole-3-carbinol Inhibits Sp1-Induced Matrix Metalloproteinase-2 Expression To Attenuate Migration and Invasion of Breast Cancer Cells - J Agric Food Chem. 2008 Dec 5 - "Indole-3-carbinol (I3C), a major indole metabolite in cruciferous vegetables, has been shown to inhibit invasion of breast cancer cells ... Migration, invasion, and MMP-2 activity of MCF-7 breast cancer cells were dose-dependently inhibited by I3C. In addition, the MMP-2 mRNA level was also reduced by I3C ... In addition, I3C inhibited the extracellular signal-regulated kinase (ERK) signaling pathway in MCF-7 cells. The results suggest that I3C inhibits MMP-2 expression by blocking the ERK/Sp1-mediated gene transcription to attenuate migration and invasion of breast cancer cells"
  • Indole-3-carbinol as a chemopreventive and anti-cancer agent - Cancer Lett. 2008 Feb 29 - "Indole-3-carbinol and its metabolite 3,3'-diindoylmethane (DIM) target multiple aspects of cancer cell-cycle regulation and survival including Akt-NFkappaB signaling, caspase activation, cyclin-dependent kinase activities, estrogen metabolism, estrogen receptor signaling, endoplasmic reticulum stress, and BRCA gene expression. This broad spectrum of anti-tumor activities in conjunction with low toxicity underscores the translational value of indole-3-carbinol and its metabolites in cancer prevention/therapy. Furthermore, novel anti-tumor agents with overlapping underlying mechanisms have emerged via structural optimization of indole-3-carbinol and DIM, which may provide considerable therapeutic advantages over the parental compounds with respect to chemical stability and anti-tumor potency. Together, these agents might foster new strategies for cancer prevention and therapy"
  • Effect of dietary soy isoflavone aglycones on the urinary 16alpha-to-2-hydroxyestrone ratio in C3H/HeJ mice - Nutr Cancer 2000;38(2):209-14 - "These data suggest that the soy isoflavonoid aglycones genistein and daidzein and indole-3-carbinol each exert a cancer-preventive effect by shifting metabolism away from the production of genotoxic metabolites toward the production of inactive metabolites"
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