Ellagic acid / ROS Cancer Research Results

EA, Ellagic acid: Click to Expand ⟱

Features:

Polyphenol found in fruits, vegetables, nuts and some mushrooms. Strawberries, raspberries, blackberries, cherries and walnuts, green tea and red wine. Pomegranate arils are a well known source.
Ellagic acid (EA) is a dietary polyphenol found in berries and pomegranate-related foods, with reported anti-inflammatory (NF-κB↓), survival-pathway suppression (PI3K/AKT↓), and anti-proliferative effects including G1 arrest and apoptosis in many cancer models. A key practical nuance is that EA/ellagitannins are extensively transformed by gut microbiota into urolithins, which are more bioavailable and may account for a large share of systemic effects.

- Ellagitannins are high molecular weight polyphenols with a complex structure that includes one or more HHDP groups attached to a sugar.
- Ellagic Acid is the simpler, bioactive compound released when the HHDP groups in ellagitannins cyclize during hydrolysis.
- one best source is raspberries. 100g gives ~50mg(reasonable dose)
- Ellagic acid has very poor oral bioavailability
- Peak plasma EA after high oral intake is typically: <50–100 nM, often much lower, this is far below concentrations used in many in-vitro anticancer studies (5–50 µM).
- efficacy depends on gut metabolism (ie ability to produce Urolithin A)
- also look at Urolithin supplements

Pathways:
Apoptosis Regulation: (Bax, Bad) (Bcl-2, Bcl-xL)
Cell Cycle Arrest: G0/G1 or G2/M phases)
NF-κB (inhibit):
MAPK Pathways: (including ERK1/2, JNK, and p38 MAPK)
PI3K/Akt/mTOR: might downregulate this pathway
p53 Pathway: may influence the expression or activation of p53
Oxidative Stress and Nrf2 Pathway:exhibits antioxidant properties, <ROS, may modulate the Nrf2 Angiogenesis Inhibition

Summary:
- Anti-oxidant and metal chelating
- with some evidence it can induce ROS in cancer tumor conditions (mitochondrial stress, redox-unstable cells)
- reported synergy with Curcumin
- Reported, reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
- Pomegranate juice (PJ) (180 ml) containing EA (25 mg) and ETs (318 mg, as punicalagins, the major fruit ellagitannin). Plasma concentration (31.9 ng/ml) after 1 h post-ingestion but was rapidly eliminated by 4 h. (Hence might be difficult to consume enough EA!!!! to match vitro requirements)
- Increased the expression of p53 and p21 proteins as well as markers of apoptosis (Bax and caspase-3), and decreases Bcl-2, NF-кB, and iNOS
- EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
- Processing methods can alter EA content; peel extraction often increases measured EA, while prolonged storage/freezing may reduce levels.

Total ellagic acid equivalents (free + bound).
Punica granatum L. Pomegranate 700mg/kg (arils), 38700mg/kg(mesocarp)
Rubus idaeus L. Raspberry 2637–3309mg/kg
jaglandaceae Walnut 410mg/kg(freeEA) 8230mg/kg(totalEA)

Ellagic acid — a naturally occurring hydrolysable polyphenol and dilactone derived from hexahydroxydiphenic acid. It occurs as free ellagic acid and, more commonly, as a structural component or hydrolysis product of ellagitannins in pomegranate, raspberries, blackberries, strawberries, walnuts, muscadine grapes, and related foods. It is formally classified as a dietary polyphenolic phytochemical rather than an approved anticancer drug. Oral EA has low aqueous solubility, limited absorption, rapid conjugation, and extensive microbiome-dependent conversion into urolithins; therefore, free EA and its microbial metabolites should be treated as related but pharmacokinetically distinct agents.

Primary mechanisms (ranked):

Induction of mitochondrial apoptosis through mitochondrial membrane depolarization, cytochrome-c release, Bax/Bcl-2 rebalancing, caspase activation, and suppression of anti-apoptotic proteins.
Suppression of PI3K/AKT/mTOR and related survival signaling, with context-dependent inhibition of STAT3, ERK, and oncogenic growth programs.
Cell-cycle arrest through p53 and p21 activation and suppression of cyclins and cyclin-dependent kinases.
Suppression of NF-κB-regulated inflammatory, survival, invasion, and cytokine programs.
Context-dependent redox modulation: antioxidant and NRF2-associated cytoprotection in normal or injured tissues, but ROS generation and oxidative mitochondrial injury in susceptible cancer cells, particularly at higher experimental concentrations or in combination treatments.
Inhibition of glycolysis and tumor pH regulation through reduced glucose utilization, lactate production, PKM2 or LDH activity, and NHE1-dependent proton extrusion in selected cancer models.
Suppression of epithelial-mesenchymal transition, migration, invasion, and metastasis through modulation of TGF-β/SMAD, Snail, β-catenin, MMP2, MMP9, and adhesion pathways.
Anti-angiogenic effects involving reduced HIF-1α, VEGF, and VEGFR2 signaling.
Context-dependent chemosensitization and radiosensitization through suppression of survival signaling, increased DNA damage or ROS, and reduced drug-resistance or EMT programs.

Bioavailability / PK relevance: Free EA has very poor oral bioavailability because of low water solubility, limited intestinal permeability, rapid methylation and glucuronidation, and short systemic persistence. Human plasma exposure to unchanged EA after ellagitannin-rich foods is generally transient and substantially below the micromolar concentrations commonly used in cancer-cell experiments. Gut bacteria convert unabsorbed EA and ellagitannins into urolithins, which circulate mainly as glucuronide or sulfate conjugates and may account for much of the systemic biological activity. Urolithin production varies markedly among individuals according to microbiome metabotype. Liposomal, nanoparticle, phospholipid, and other delivery systems improve exposure experimentally, but none has established clinical anticancer efficacy.

In-vitro vs systemic exposure relevance: Many anticancer studies use approximately 5–100 µM EA for hours to days. These concentrations commonly exceed achievable circulating free-EA exposure after food or conventional oral supplementation. Direct relevance is greater for gastrointestinal luminal exposure, local tissue exposure, specialized formulations, or experiments involving metabolites. Results obtained at high micromolar concentrations should not be interpreted as evidence that an ordinary dietary dose will produce equivalent systemic tumor effects.

Clinical evidence status: Predominantly preclinical. EA has extensive cell-culture evidence and several animal tumor studies, but human oncology evidence remains limited to an older small adjunctive prostate-cancer trial, observational or combination-product studies, tissue-disposition studies, and trials of ellagitannin-rich pomegranate, berry, or muscadine extracts. These mixed extracts cannot establish EA-specific efficacy. Human randomized trials in metabolic, inflammatory, gastrointestinal, and neurologic conditions provide preliminary safety and biomarker data but do not validate EA as a cancer treatment. EA is not an FDA-approved anticancer agent and should be classified as investigational or dietary adjunct evidence, not established oncology therapy.

Safety / interaction constraints: Food-derived exposure is generally well tolerated, and small supplementation trials have not identified a consistent major toxicity signal. Long-term safety of purified high-dose EA in oncology populations is insufficiently characterized. Potential interaction concerns include inhibition or modulation of drug-metabolizing enzymes and transporters, antiplatelet activity, and uncertain effects when combined with cytotoxic chemotherapy or radiotherapy. The antioxidant-versus-pro-oxidant direction is dose-, tissue-, and treatment-dependent; concurrent use during cancer therapy therefore requires clinical review rather than assuming either protection or sensitization.

Ellagic Acid Mechanistic Profile

Rank	Pathway / Axis	Cancer Cells	Normal Cells	TSF	Primary Effect	Notes / Interpretation
1	Mitochondrial apoptosis	Mitochondrial membrane potential ↓; Bax and cytochrome-c ↑; Bcl-2 and Bcl-xL ↓; caspase-3 and caspase-9 ↑	Apoptotic injury ↓ or ↔ (context-dependent)	R, G	Programmed tumor-cell death	A recurrent downstream mechanism, usually following survival-pathway inhibition, mitochondrial stress, or ROS accumulation.
2	PI3K AKT mTOR survival signaling	PI3K ↓; phosphorylated AKT ↓; mTOR ↓; PTEN ↑ (model-dependent)	AKT survival signaling ↔ or ↑ during tissue injury (context-dependent)	R, G	Growth and survival suppression	The direction can differ in nonmalignant injury models, where EA may preserve physiological AKT signaling.
3	Cell-cycle and p53 p21 control	p53 ↑; p21 ↑; cyclin D1 and cyclin E ↓; CDK2, CDK4, and CDK6 ↓; arrest ↑	Aberrant proliferation ↓; normal cycling cells usually less affected	G	Cytostasis and apoptosis priming	G0/G1 arrest is frequent, although G2/M or S-phase effects occur depending on tumor type and exposure.
4	NF-κB inflammatory survival signaling	NF-κB activation ↓; COX-2 ↓; iNOS ↓; IL-6 and IL-8 ↓; anti-apoptotic transcription ↓	Inflammatory signaling ↓	R, G	Anti-inflammatory and anti-survival activity	NF-κB suppression can contribute to reduced proliferation, invasion, treatment resistance, and inflammatory cytokine production.
5	Mitochondrial ROS increase	ROS ↑; oxidative DNA damage ↑; mitochondrial stress ↑ (dose-dependent)	ROS injury ↓ or ↔ through antioxidant activity (context-dependent)	P, R	Selective oxidative stress	Pro-oxidant effects are most evident in redox-unstable cancer cells, high-concentration experiments, and combination treatments. EA is not uniformly pro-oxidant.
6	NRF2 antioxidant response	NRF2 and HO-1 ↔, ↑, or ↓ (model-dependent)	NRF2 ↑; HO-1 and antioxidant enzymes ↑; lipid peroxidation ↓	R, G	Secondary redox adaptation	Normal-tissue protection is relatively consistent, whereas cancer-cell NRF2 modulation is heterogeneous and may depend on baseline NRF2 activity.
7	Glycolysis and intracellular pH regulation	Glucose consumption ↓; lactate production ↓; LDH and PKM2 ↓; NHE1 ↓; intracellular pH ↓ (model-dependent)	↔	R, G	Metabolic restriction and acidification	Demonstrated in selected cancer models and should not be generalized to every tumor type.
8	STAT3 and MAPK growth signaling	STAT3 ↓; phosphorylated STAT3 ↓; ERK signaling ↓; JNK or p38 modulation (context-dependent)	Stress-responsive MAPK signaling ↔ or normalized	R, G	Proliferation and survival inhibition	MAPK direction varies with tumor type, concentration, and whether stress-mediated apoptosis is being induced.
9	EMT invasion and metastasis	TGF-β and SMAD signaling ↓; Snail and Twist ↓; vimentin ↓; E-cadherin ↑; MMP2 and MMP9 ↓	Pathological matrix remodeling ↓	G	Reduced migration and invasion	Includes reversal of EMT and, in some models, partial resensitization of drug-resistant cancer cells.
10	HIF-1α VEGF angiogenesis	HIF-1α ↓; VEGF ↓; VEGFR2 signaling ↓; angiogenesis ↓	Pathological angiogenesis ↓; physiological effect uncertain	G	Anti-angiogenic activity	Supported mainly by cell, endothelial-assay, and animal evidence rather than validated clinical anti-angiogenic activity.
11	DNA damage and repair balance	Oxidative DNA damage ↑; PARP cleavage ↑; p53-dependent damage response ↑ (dose-dependent)	Genotoxic injury ↓ through antioxidant and antimutagenic activity (context-dependent)	R, G	Tumor-cell damage with normal-cell protection potential	The bidirectional profile reflects differing redox conditions and exposure levels in malignant versus normal systems.
12	Chemosensitization	Drug sensitivity ↑; EMT and survival signaling ↓; apoptosis ↑ (combination-dependent)	Chemotherapy-associated injury may ↓ in some models	R, G	Adjunctive treatment modulation	Reported with agents including gemcitabine and several experimental combinations. Clinical confirmation is inadequate.
13	Radiosensitization	Radiation response ↑; ROS and DNA damage ↑; clonogenic survival ↓ (model-dependent)	Radiation injury may ↓ through antioxidant and anti-inflammatory effects (model-dependent)	P, R, G	Differential radiation response	Recent preclinical work supports possible simultaneous tumor sensitization and normal-tissue protection, but this has not been established clinically.
14	Microbiome conversion to urolithins	Direct EA exposure limited; systemic effects may be mediated partly by urolithin metabolites	Urolithin production and conjugate exposure vary markedly among individuals	G	Metabolite-dependent systemic activity	Metabotype 0, A, or B and microbial composition can materially alter metabolite identity, quantity, and biological response.
15	Clinical Translation Constraint	Free EA exposure commonly below active in-vitro concentrations; tumor delivery unproven	Food exposure generally tolerated; high-dose long-term safety and drug interactions incompletely defined	G	Bioavailability and evidence limitation	Poor solubility, rapid metabolism, microbiome heterogeneity, mixed-extract trials, limited oncology RCT evidence, and lack of an approved pharmaceutical formulation restrict translation.

TSF: P: 0–30 min R: 30 min–3 hr G: >3 hr

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)

"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⟱

1615-

EA,

Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum l.) polyphenols after ingestion of a standardized extract in healthy human volunteers

Human,

Nor,

*BioAv∅, *ROS∅,

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,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv∅, 1,
Total Targets: 2

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