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| Names | |
|---|---|
| Preferred IUPAC name (1H-Indol-3-yl)methanol | |
| Other names Indole-3-carbinol; 3-Indolylcarbinol; 1H-Indole-3-methanol; 3-Hydroxymethylindole; 3-Indolemethanol; Indole-3-methanol; I3C | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| ECHA InfoCard | 100.010.762 |
| EC Number |
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| RTECS number |
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| UNII | |
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| Properties | |
| C9H9NO | |
| Molar mass | 147.177 g·mol−1 |
| Appearance | Off-white solid |
| Melting point | 96 to 99 °C (205 to 210 °F; 369 to 372 K) |
| Partially in cold water[vague] | |
| Hazards | |
| GHS labelling:[2] | |
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| Warning | |
| H315,H319 | |
| P305+P351+P338 | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Indole-3-carbinol (I3C,C9H9NO) is produced by the breakdown of theglucosinolateglucobrassicin, which can be found at relatively high levels incruciferous vegetables such asbroccoli,cabbage,cauliflower,brussels sprouts,collard greens andkale. It is also available indietary supplements.[3] Indole-3-carbinol is the subject of on-goingbiomedical research into its possibleanticarcinogenic,[4]antioxidant, and anti-atherogenic effects.[5] Research on indole-3-carbinol has been conducted primarily usinglaboratory animals andcultured cells.[6] Limited and inconclusive human studies have been reported. A recent review of the biomedical research literature found that "evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent" and "largerrandomized controlled trials are needed" to determine if supplemental indole-3-carbinol has health benefits.[7]
Investigation of mechanisms by which consumption of indole-3-carbinol might influencecancer incidence focuses on its ability to alterestrogenmetabolism and other cellular effects. Controlled studies have been performed on such animals asrats,mice, andrainbow trout, introducing various controlled levels ofcarcinogens, and levels of indole-3-carbinol into their daily diet. Results showed dose-related decreases intumor susceptibility due to indole-3-carbinol (inferred by decreases inaflatoxin–DNA binding). The first direct evidence of pure anti-initiating activity by a naturalanticarcinogen (indole-3-carbinol) found in human diet was claimed by Dashwoodet al. in 1989.[8]
Indole-3-carbinol induces aG1 growth arrest of human reproductive cancer cells.[9] This is potentially relevant to the prevention and treatment of cancer, as theG1 phase ofcell growth occurs early in the cell life cycle, and, for most cells, is the major period ofcell cycle during its lifespan. The G1 phase is marked by synthesis of various enzymes that are required in the next ("S") phase, including those needed for DNA replication.
Overuse of indole-3-carbinol supplements in the hope of preventing cancer may be unwise, as the hormone balance should be tested (via simple blood test) before regular consumption. Such caution is advised, due to its effect onestrogen levels (estrogen has a significant impact on brain function).[10][11]
It promotes liver cancer introut when it is combined withaflatoxin B1 and demotesmetastasis.[6]
Indole-3-carbinol causes proliferation arrest andapoptosis in humanmelanoma cells. Kimet al. (2011) showed that the master regulator of melanoma biology,microphthalmia-associated transcription factor (MITF-M) was downregulated by indole-3-carbinol to induce apoptosis.[12] Kunduet al. (2017) demonstrated that the anticancer property of indole-3-carbinol is driven by specific targeting of oncogenic pathways.[13][14] In two different studies using xenografted mouse model of melanoma, they observed that subcutaneous injection of indole-3-carbinol could bring down tumor burden significantly. The underlying molecular mechanism of this anti-tumor effect was found to be by the specific inhibition of activity of oncogenicBRAFV600E in tumors that harbored the mutation. However, in tumors that expressed wild type BRAF, indole-3-carbinol did not cause any comparable antiproliferative effect. Additionally indole-3-carbinol did not cause antiproliferation even in normal epidermal melanocytes underscoring the specificity and selectivity of its action. Kunduet al.[citation needed] further showed that inhibition of BRAF V600E activity by indole-3-carbinol resulted in downregulation of MITF-M by downstream signaling which caused a G1cell cycle arrest leading to the observed antiproliferative effect.
In a second study Kunduet al.[citation needed] showed that in melanoma cells wherePTEN is downregulated, indole-3-carbinol directly interacts withNEDD41 to prevent PTEN ubiquitination and subsequent proteasomal degradation. This results in stabilization of PTEN and inhibition of proliferation by downstreamAKT signaling. Overall scientific evidence shows that in melanoma, indole-3-carbinol specifically inhibits the two most commonly associated driver mutation signaling pathways to cause proliferation, a fact that can be used to design clinical trial to treat human patients with indole-3-carbinol in future.
Indole-3-carbinol can shiftestrogen metabolism towards less estrogenic metabolites.Systemic lupus erythematosus (SLE, or lupus), anautoimmune disease, is associated with estrogen. In a study using mice bred to develop lupus, indole-3-carbinol was fed to one group while another group was fed a standard mouse diet; the group fed the indole-3-carbinol diet lived longer and had fewer signs of disease.[15]
Another study of lupus-prone mice with indole-3-carbinol defined the mechanism for the improvement of their disease to be due to sequential blocks in the development ofB andT cells of these mice. The maturation arrests resulted in a fall inautoantibody production, thought to be a crucial component of lupus causation. In addition, I3C supplementation of the disease prone mice led to a normalization of their T cell function.[16]
Women with lupus can manifest a metabolic response to indole-3-carbinol and might also benefit from its antiestrogenic effects. Clinical trials are currently underway to determine the efficacy of treating human patients with lupus using indole-3-carbinol.
There is evidence suggesting that indole-3-carbinol may have an effect onhuman papillomavirus-infected cells in both pediatrics and adult patients.[17][18] Research is ongoing.
