Indole-3-carbinol / TumCI Cancer Research Results

I3C, Indole-3-carbinol: Click to Expand ⟱

Features:

Found in broccoli, cabbage, cauliflower, brussel sprouts, collard greens and kale.

Estimated DIM Exposure from Common Cruciferous Vegetables

Vegetable	Typical Serving	Glucobrassicin / I3C Precursor	Expected DIM Production	Human Evidence	Practical Interpretation
Brussels sprouts	50–100 g	High ~184 µmol glucobrassicin/100 g reported in a controlled human feeding study	High relative to most common crucifers	Strongest direct evidence. 50 g raw Brussels sprouts produced readily measurable urinary DIM. Individual 24-h urinary DIM ranged approximately 1.4–44 pmol/mg creatinine.	Probably one of the most effective ordinary foods for producing I3C-derived DIM. Raw or lightly cooked sprouts that retain myrosinase are preferable.
Cabbage	50–100 g	Moderate ~46 µmol glucobrassicin/100 g in the controlled feeding study	Low–moderate	Direct human evidence. 50 g raw cabbage generated measurable DIM, but approximately several-fold less than the high-glucobrassicin Brussels sprouts used in the same trial.	Effective dietary source, although cultivar strongly affects glucobrassicin concentration.
Broccoli	75–100 g	Moderate–high but extremely variable by cultivar published glucobrassicin concentrations span a very wide range	Moderate–high potential	Glucobrassicin and I3C formation are well established, but precise DIM production after a normal broccoli serving has not been quantified as well as Brussels sprouts/cabbage.	Potentially a very useful DIM-producing food. Broccoli is better known for glucoraphanin/sulforaphane, but some cultivars are also rich in glucobrassicin.
Cauliflower	100 g	Low–moderate glucobrassicin is present but generally lower than in high-glucobrassicin Brussels sprouts	Low–moderate potential	Direct quantitative human DIM data are limited.	Likely contributes meaningful I3C/DIM exposure but is not generally considered the richest dietary source.
Collard greens	75–100 g	Variable indole-glucosinolate content	Low–moderate potential	No good controlled human study directly quantifying DIM generated from a standard collard-green serving.	Likely contributes to DIM exposure, but current evidence does not support assigning a precise mg DIM equivalent.
Kale	75–100 g	Moderate indole-glucosinolate content ~1 µmol/g dry weight glucobrassicin reported in some kale cultivars	Low–moderate potential	No strong human study directly quantifying DIM after a typical kale serving.	Useful dietary source, although glucobrassicin content is highly cultivar-dependent and may be lower than Brussels sprouts.

Important: vegetables do not normally contain large amounts of preformed DIM. They contain glucobrassicin, which is converted by myrosinase to indole-3-carbinol (I3C); I3C then undergoes acid condensation in the stomach to DIM and other oligomers. Therefore, glucobrassicin content is a better measure of dietary DIM-producing potential than the amount of DIM present in the vegetable itself.

Cruciferous Vegetable Exposure Compared with Research I3C Doses

Source	Typical Amount	Approximate Glucobrassicin	Maximum Theoretical I3C Equivalent	Relative to 200 mg I3C	Relative to 400 mg I3C	Interpretation
Brussels sprouts	50 g raw	~92 µmol	~13.5 mg	~7%	~3%	Direct human feeding data; produces readily measurable urinary DIM.
Brussels sprouts	100 g raw	~184 µmol	~27 mg	~14%	~7%	A relatively high dietary exposure, but still substantially below purified-I3C clinical doses.
Cabbage	50 g raw	~23 µmol	~3.4 mg	~2%	<1%	Direct human data show measurable DIM formation despite the relatively low precursor dose.
Cabbage	100 g raw	~46 µmol	~6.8 mg	~3%	~2%	Useful dietary exposure but far below pharmacological I3C dosing.
Broccoli	~100 g	Highly cultivar-dependent	Often roughly several to tens of mg	Usually <10%	Usually <5%	Some high-glucobrassicin cultivars may approach Brussels sprouts; ordinary broccoli varies greatly.
Broccoli microgreens	~25–50 g fresh	Highly variable with cultivar and harvest age	Usually low-to-tens of mg range	Typically <10%	Typically <5%	Potentially concentrated relative to mature vegetables, but published values are too variable to assign a universal I3C equivalent.
Kale / collards / cauliflower	~75–100 g	Low to moderate and variable	Usually several mg to low-tens of mg	Usually <10%	Usually <5%	Meaningful dietary sources but generally not comparable with pharmacological I3C dosing.
Human vegetable dose-ranging study	Cabbage + Brussels sprouts	25–500 µmol	~3.7–73.6 mg	~2–37%	~1–18%	Urinary DIM increased with glucobrassicin dose, demonstrating biological uptake across this dietary range.
Purified I3C clinical trial	200 mg/day	Not applicable	200 mg administered I3C	100%	50%	CIN II–III trial; clinical lesion regression was reported in a small randomized study.
Purified I3C clinical trial	300 mg/day	Not applicable	300 mg administered I3C	150%	75%	Approximately the minimum dose associated with a significant estrogen-metabolism biomarker response in one dose-ranging study.
Purified I3C clinical trial	400 mg/day	Not applicable	400 mg administered I3C	200%	100%	Common human research dose producing substantial pharmacodynamic effects.
Purified I3C phase I	800 mg/day	Not applicable	800 mg administered I3C	400%	200%	Produced marked CYP1A2 induction; pharmacological rather than dietary exposure.

Important: The theoretical I3C equivalents above are stoichiometric upper-bound comparisons, not measurements of absorbed I3C. Vegetable glucobrassicin must first be hydrolyzed by myrosinase, and I3C subsequently undergoes rapid gastric condensation into DIM and multiple other products. Therefore, 27 mg theoretical I3C from Brussels sprouts should not be interpreted as pharmacokinetically identical to swallowing 27 mg purified I3C.

Best approximate ranking for DIM production: Brussels sprouts > high-glucobrassicin broccoli > cabbage ≈ kale > cauliflower ≈ collard greens, but cultivar and preparation can change this order substantially.

Indole-3-carbinol — Indole-3-carbinol (I3C; indole-3-methanol; 3-hydroxymethylindole) is a naturally occurring indole phytochemical generated from the glucosinolate glucobrassicin when cruciferous vegetables are disrupted and plant myrosinase hydrolyzes the glucosinolate. It is classified as a dietary phytochemical and investigational chemopreventive agent rather than an approved anticancer drug. Major food sources include broccoli, Brussels sprouts, cabbage, cauliflower, kale, collards, and related Brassica vegetables. I3C is chemically unstable in gastric acid and rapidly forms multiple condensation products, particularly 3,3'-diindolylmethane (DIM); consequently, many systemic biological effects after oral I3C administration may actually be mediated by DIM and other acid-derived products rather than circulating parent I3C.

Primary mechanisms (ranked):

Inhibition of proliferative and survival signaling, particularly PI3K/AKT and NF-κB, with downstream suppression of anti-apoptotic proteins and promotion of apoptosis.
G1 cell-cycle arrest through modulation of cyclins, cyclin-dependent kinases, p21/p27, and retinoblastoma signaling.
Activation/modulation of the aryl hydrocarbon receptor (AhR), including induction of CYP1-family enzymes and context-dependent pro-apoptotic transcriptional responses.
Mitochondrial apoptosis involving ↑ Bax/Bcl-2 ratio, mitochondrial membrane disruption, cytochrome-c release, and caspase activation.
Suppression of Wnt/β-catenin signaling, reducing proliferation, epithelial-mesenchymal transition, migration, and invasion in susceptible tumor models.
Modulation of estrogen signaling and metabolism, including AhR-dependent ERα degradation and increased estrogen 2-hydroxylation.
PTEN upregulation with suppression of tumor growth and enhancement of antitumor immune responses in recent colorectal-cancer models; this remains preclinical.
Secondary/context-dependent oxidative-stress signaling, including ROS-dependent ATF3/NOXA-mediated apoptosis in some breast-cancer models; ROS modulation is not uniformly pro-oxidant across tissues or experimental systems.

Bioavailability / PK relevance: Oral I3C has unusual pharmacokinetics because acidic gastric conditions convert it rapidly into oligomeric products. In human pharmacokinetic studies, parent I3C was not detectable in plasma; DIM was the principal measurable circulating I3C-derived compound. After single oral doses of 400–1000 mg I3C, DIM exposure increased markedly, with an approximate Tmax of 2 hours, but exposure plateaued above about 1000 mg. Thus, oral I3C should be viewed pharmacologically as a precursor mixture that generates DIM and additional condensation products in the gastrointestinal tract rather than as a conventional systemically available parent compound.

In-vitro vs systemic exposure relevance: Many direct anticancer experiments expose cultured cells to I3C concentrations in the tens to hundreds of micromolar range, frequently around 100–300 µM. These concentrations substantially exceed plausible circulating parent-I3C exposure because parent I3C is generally undetectable after oral administration. Therefore, direct high-concentration I3C cytotoxicity in vitro has limited systemic PK relevance. Effects mediated by locally generated gastric products such as DIM, or by enzyme/receptor modulation occurring during gastrointestinal and hepatic exposure, are more biologically plausible after oral supplementation.

Clinical evidence status: Small human studies and early randomized trials are available, but there is no established clinical evidence that I3C treats invasive cancer. A small placebo-controlled randomized trial in cervical intraepithelial neoplasia II–III reported greater lesion regression with 200 or 400 mg/day I3C than placebo over 12 weeks. Phase-I studies in women found 400–800 mg/day generally tolerable and demonstrated substantial induction of CYP1A2 and altered estrogen metabolism. Evidence for established cancer therapy remains preclinical; recent reports of PTEN induction and enhancement of anti-PD-1 therapy are animal-model findings. I3C is not an approved anticancer therapy and should presently be categorized primarily as an investigational chemopreventive/pharmacologic dietary compound.

Indole-3-carbinol Cancer-Relevant Mechanisms

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Primary Effect	Notes / Interpretation
1	PI3K / AKT / NF-κB survival signaling	↓ AKT ↓ NF-κB ↓ IKK ↓ anti-apoptotic signaling	Less pronounced or ↔ in some non-tumorigenic epithelial models	↓ survival ↑ apoptosis ↑ chemosensitivity	One of the most repeatedly demonstrated I3C anticancer axes. Tumor-cell selectivity has been reported in paired malignant and nonmalignant breast epithelial models, but it is model-dependent.
2	Cell-cycle control	↓ cyclin D1 ↓ cyclin E ↓ CDK2/CDK4/CDK6 ↑ p21/p27 ↓ Rb phosphorylation	Usually less growth inhibition (model-dependent)	G1 arrest ↓ proliferation	G1 arrest is a consistent phenotype across several breast, prostate, leukemia, and other cancer models.
3	Mitochondrial intrinsic apoptosis	↑ Bax/Bcl-2 ratio ↓ mitochondrial membrane potential ↑ cytochrome-c release ↑ caspases	Bax translocation may occur without full mitochondrial collapse or apoptosis in some normal epithelial cells	↑ apoptotic cell death	Provides evidence for partial tumor selectivity: mitochondrial depolarization and downstream apoptosis can be substantially stronger in malignant cells.
4	AhR signaling	↑ AhR activity ↑ CYP1A1 context-dependent ↑ apoptosis	↑ xenobiotic-response enzymes	Transcriptional reprogramming chemoprevention or apoptosis	AhR activation contributes directly to cytotoxicity in some colorectal and breast-cancer models. AhR biology is strongly tissue- and ligand-dependent and can also support tumorigenesis in other contexts.
5	Wnt / β-catenin signaling	↓ β-catenin ↓ c-Myc ↓ cyclin D1 ↓ EMT	Insufficient comparative evidence	↓ proliferation ↓ migration ↓ invasion	Supported by recent esophageal squamous-cell carcinoma experiments in vitro and xenografts and by earlier prostate-cancer studies.
6	Estrogen receptor and estrogen metabolism	↓ ERα (context-dependent) ↓ estrogen-dependent proliferation	↑ CYP1A2/CYP1-family activity ↑ estrogen 2-hydroxylation	Altered estrogen signaling and metabolism	I3C can trigger AhR-dependent ERα degradation in ER-positive breast-cancer cells. Human supplementation substantially changes estrogen-metabolite ratios, but whether this reduces cancer incidence has not been established.
7	PTEN / PI3K-AKT and antitumor immunity	↑ PTEN ↓ proliferation/migration ↑ CD8+ T-cell infiltration	Insufficient comparative evidence	↓ tumor progression ↑ anti-PD-1 response	Recent colorectal-cancer study demonstrated PTEN induction and potentiation of PD-1 antibody therapy in immunocompetent mice. This remains preclinical.
8	Oxidative stress and ROS signaling	↑ ROS (context-dependent) ↑ ATF3 ↑ NOXA	ROS may ↓ in other injury models	Secondary promotion of apoptosis	Not a universal I3C mechanism. Pro-oxidant signaling contributes to apoptosis in selected cancer models, whereas antioxidant and NRF2-related effects occur in other biological contexts.
9	Migration and invasion	↓ EMT ↓ migration ↓ invasion	Insufficient comparative evidence	↓ metastatic phenotype	Likely downstream of several mechanisms including β-catenin, AKT/NF-κB, mitochondrial stress, and altered transcription rather than a single independent target.
10	Chemosensitization and immunotherapy sensitization	↑ sensitivity (agent- and model-dependent)	Variable	Potential adjunctive activity	Preclinical enhancement has been reported with several cytotoxic drugs and, more recently, anti-PD-1 therapy. These combinations are not clinically validated.
11	Clinical Translation Constraint	High-concentration effects often difficult to reproduce systemically	↑ CYP1A2 and other xenobiotic metabolism may alter drug exposure	Limits direct translation of cell-culture results	Parent I3C is acid-labile and essentially undetectable in human plasma after oral administration. DIM and other condensation products dominate systemic exposure. Many in-vitro I3C experiments use approximately 100–300 µM, making direct parent-compound cytotoxicity pharmacokinetically questionable. CYP1A2 induction creates a clinically relevant drug-interaction concern.

TumCI, Tumor Cell invasion: Click to Expand ⟱

Source:

Type:

Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms:

1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion.

2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue.

3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment.

4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream.

5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body.

6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection.

7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs.

8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.

Scientific Papers found: Click to Expand⟱

7592-

I3C,

Indole-3-carbinol as a chemopreventive and anti-cancer agent

Review,

Var,

JNK↑, STAT3↓, TumCCA↑, P21↑, p27/CDKN1B↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, AhR↑, ER-α36↓, ChemoSen↑, ER Stress↑, UPR↑, BRCA1↑, BRCA2↑, TumCMig↓, TumCI↓, VEGF↓, IL8↓, MMP2↓, MMP9↓, RadioS↑, Akt↓, NF-kB↓, DR4↑, DR5↑,

7584-

I3C,

Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells

in-vitro,

Cerv,

HeLa

in-vitro,

CRC,

HCT8

in-vitro,

Liver,

HepG2

TumCP↓, Apoptosis↑, TumCI↓, *antiOx↑, AhR↑, MMP↓, Casp3↑, Casp8↑,

7582-

I3C,

Indole-3-Carbinol Promotes Apoptosis and Inhibits the Metastasis of Esophageal Squamous Cell Carcinoma by Downregulating the Wnt/β-Catenin Signaling Pathway

vitro+vivo,

ESCC,

nude BALB/c mice bearing EC18 xenografts were treated with I3C and/or LiCl.

Apoptosis↑, TumCMig↓, TumCI↓, β-catenin/ZEB1↓, cMyc↓, cycD1/CCND1↓,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:

Clinical Biomarkers(tgid=22) ⓘ

BRCA1↑, 1,
Total Targets: 36

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,
Total Targets: 1

Scientific Paper Hit Count for: TumCI, Tumor Cell invasion

3 Indole-3-carbinol

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:99  Target#:324  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Indole-3-carbinol / TumCI Cancer Research Results

Estimated DIM Exposure from Common Cruciferous Vegetables

Cruciferous Vegetable Exposure Compared with Research I3C Doses

Indole-3-carbinol Cancer-Relevant Mechanisms

Pathway results for Effect on Cancer / Diseased Cells:

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

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