Indole-3-carbinol / ROS 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.

ROS, Reactive Oxygen Species: Click to Expand ⟱

Source: HalifaxProj (inhibit)

Type:

Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)
ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy

ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination


Item  ROS↑  NRF2  Condition  Mechanism Class  Remarks  

ROS">Piperlongumine
+++  ↓  [D][T]  ROS-dominant
Selective <span class="wphighlight">ROS</span> stressor, Prevents compensatory upregulation of NRF2, ie GSH↓



ROS">Shikonin
+++ ↓/± [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + glycolysis + GPX4 inhibition



ROS">Vitamin K3 (menadione)
+++ ↓ [D] ROS-dominant
Quinone redox cycler; toxicity limits use



ROS">Copper (ionic / nano)
+++ ↓ [Fe][F] ROS-dominant
Fenton-type redox chemistry



ROS">Sodium Selenite
+++ ↓ [D] ROS-dominant
Pro-oxidant, depletes GSH



ROS">Juglone
+++ ↓ [D] ROS-dominant
Strong quinone <span class="wphighlight">ROS</span> chemistry



ROS">Auranofin
+++ ↓ [D] ROS-dominant
TrxR inhibition → redox collapse



ROS">Photodynamic Therapy (PDT)
+++ 0 [L][O₂] ROS-dominant
Singlet oxygen is core cytotoxic mechanism



ROS">Radiotherapy / Radiation
+++ 0 [O₂] ROS-dominant
DNA damage largely via <span class="wphighlight">ROS</span>



ROS">Doxorubicin
+++ ↓ [D] ROS-dominant
Chemo; redox cycling + mitochondrial <span class="wphighlight">ROS</span>



ROS">Cisplatin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> contributes to DNA/protein damage



ROS">Salinomycin
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated CSC toxicity



ROS">Artemisinin / DHA
++ ↓ [Fe][T] ROS-dominant
Iron-activated radical generation



ROS">Sulfasalazine
++ ↓ [C][T] ROS-dominant
Ferroptosis; xCT inhibition → lipid <span class="wphighlight">ROS</span>



ROS">FMD / fasting
++ ↓ [M][C][O₂] ROS-dominant
Metabolic stress → mitochondrial <span class="wphighlight">ROS</span>



ROS">Vitamin C (pharmacologic)
++ ↓ [Fe][D] ROS-dominant
Extracellular H₂O₂ at high dose



ROS">Silver nanoparticles
++ ± [F][D] ROS-dominant
<span class="wphighlight">ROS</span> common; selectivity unreliable



ROS">Gambogic acid
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Parthenolide
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span> + NF-κB suppression



ROS">Plumbagin
++ ↓ [D] ROS-dominant
Quinone <span class="wphighlight">ROS</span> driver



ROS">Allicin
++ ↓ [D] ROS-dominant
Thiol-reactive oxidative stress



ROS">Ashwagandha (Withaferin A)
++ ↓ [D][T] ROS-dominant
<span class="wphighlight">ROS</span>-mediated apoptosis



ROS">Berberine
++ ↓ [D][M] ROS-dominant
Mitochondrial <span class="wphighlight">ROS</span> induction



ROS">PEITC
++ ↓ [D][C] ROS-dominant
GSH depletion + <span class="wphighlight">ROS</span>



ROS">Methionine restriction
+ ↓ [M][C][T] ROS-secondary
Redox vulnerability increased; <span class="wphighlight">ROS</span> indirect



ROS">DCA
+ ± [M][T] ROS-secondary
<span class="wphighlight">ROS</span> via forced OXPHOS



ROS">Capsaicin
+ ± [D][T] ROS-secondary
Ca²⁺ stress → <span class="wphighlight">ROS</span>



ROS">Galloflavin
+ 0 [D] ROS-secondary
<span class="wphighlight">ROS</span> not primary driver



ROS">Piperine
+ ± [D][F] ROS-secondary
Weak <span class="wphighlight">ROS</span> induction



ROS">Propyl gallate
+ ↓ [D] ROS-secondary
Pro-oxidant at high dose



ROS">Scoulerine
+ ? [D][T] ROS-secondary
Sparse <span class="wphighlight">ROS</span> data



ROS">Thymoquinone
± ± [D][T] Dual redox
Antioxidant ↔ pro-oxidant switch



ROS">Emodin
± ± [D][T] Dual redox
Not cancer-exclusive



ROS">Alpha-lipoic acid (ALA)
± ↑ [D][M] NRF2-dominant
Antioxidant at low dose



ROS">Curcumin
± ↑/↓ [D][F] NRF2-dominant
Hormetic redox behavior



ROS">EGCG
± ↑/↓ [D][O₂] NRF2-dominant
Auto-oxidation artifacts common



ROS">Quercetin
± ↑/↓ [D][Fe] NRF2-dominant
GSH-dependent cycling



ROS">Resveratrol
± ↑ [D][M] NRF2-dominant
<span class="wphighlight">ROS</span> only at high dose



ROS">Sulforaphane
± ↑↑ [D] NRF2-dominant
Strong NRF2 activator



ROS">Lycopene
0 ↑ — Antioxidant
Consistently antioxidant



ROS">Rosmarinic acid
0 ↑ — Antioxidant
Primarily antioxidant



ROS">Citrate
0 0 — Neutral
Metabolic; not a <span class="wphighlight">ROS</span> agent

Scientific Papers found: Click to Expand⟱

7600-

I3C,

Indole-3-Carbinol (I3C) and its Major Derivatives: Their Pharmacokinetics and Important Roles in Hepatic Protection

Review,

Nor,

*ROS↓, *hepatoP↑, *AntiTum↑, *Imm↑, *Inflam↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Total Targets: 0

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

Imm↑, 1, Inflam↓, 1,

Functional Outcomes(tgid=23) ⓘ

AntiTum↑, 1, hepatoP↑, 1,
Total Targets: 5

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species

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#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid