Ellagic acid / P53 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,
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)

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 NF-κB inflammatory transcription NF-κB ↓; pro-inflammatory cytokine programs ↓ (context) Inflammation tone ↓ R, G Anti-inflammatory / anti-survival transcription EA is repeatedly reported to suppress NF-κB activity and reduce inflammatory cytokine expression in tumor and inflammation models.
2 PI3K → AKT (± mTOR) survival axis PI3K/AKT ↓ (reported); proliferation ↓ ↔ R, G Growth/survival suppression Multiple cancer studies/reviews report EA-associated suppression of PI3K/AKT signaling linked to G1 arrest and apoptosis.
3 Cell-cycle control (G1 arrest emphasis) Cell-cycle arrest ↑ (often G1); Cyclin/CDK programs ↓ (context) ↔ G Cytostasis Frequently observed as a later phenotype-level outcome; commonly reported alongside reduced proliferation.
4 Intrinsic apoptosis (mitochondrial / caspase-linked) Apoptosis ↑; caspase activation ↑ (context) ↔ (generally less activation) G Apoptosis execution Often downstream of survival signaling suppression and/or stress signaling; reported across multiple tumor types.
5 Nrf2 antioxidant response (Keap1/Nrf2/ARE) Stress adaptation modulation (context-dependent) Nrf2 ↑; antioxidant enzymes ↑ (context) R, G Endogenous antioxidant upshift EA is commonly described as activating Nrf2/ARE programs in oxidative-stress models; tumor direction is model-dependent and should not be overstated.
6 ROS / oxidative stress Oxidative stress tone ↓ (often); ROS direction can vary by model ROS injury ↓ P, R, G Redox buffering (context-dependent) EA is widely characterized as antioxidant/anti-inflammatory; in cancer models, oxidative stress effects can be secondary to pathway reprogramming.
7 Invasion / metastasis programs (MMPs / EMT) MMPs ↓; migration/invasion ↓ (reported) ↔ G Anti-invasive phenotype Often reported as downstream outcomes tied to NF-κB and survival signaling changes; keep as “reported” (not universal).
8 Angiogenesis signaling (VEGF & angiogenic outputs) VEGF ↓; angiogenic outputs ↓ (reported) ↔ G Anti-angiogenic support Typically observed as later reductions in pro-angiogenic expression/secretion or angiogenesis assays.
9 One-carbon / microbiome conversion to urolithins (translation driver) Systemic activity often mediated by urolithins (e.g., urolithin A) rather than free EA — — PK / metabolite constraint EA and ellagitannins are transformed by gut microbiota into urolithins, bioavailable metabolites; inter-individual variation in “metabotypes” affects exposure and effects.
10 Bioavailability constraint (oral exposure) Free EA systemic exposure often limited (without formulation / metabolite reliance) — — Translation constraint EA has absorption/metabolism constraints; measuring metabolites (urolithins) is often more informative than EA alone.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (primary/rapid effects; early redox interactions)
  • R: 30 min–3 hr (acute stress-response + transcription signaling shifts)
  • G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)
P53, P53-Guardian of the Genome: Click to Expand ⟱
Source: TCGA
Type: Proapototic
TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.
Scientific Papers found: Click to Expand⟱
1609- CUR,  EA,    Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells
- in-vitro, Cerv, NA
eff↑, Dose∅, ROS↑, DNAdam↑, P53↑, P21↑, BAX↑, Dose∅,
1620- EA,  Rad,    Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study
- in-vitro, Liver, HepG2
ROS↑, P53↑, TumCCA↑, IL6↓, COX2↓, TNF-α↓, MMP↓, angioG↓, MMP9↓, BAX↑, Casp3↑, Apoptosis↑, RadioS↑, TBARS↑, GSH↓, Bax:Bcl2↑, p‑NF-kB↓, p‑STAT3↓,
1605- EA,    Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence
- Review, Var, NA
*BioAv↓, antiOx↓, Inflam↓, TumCP↓, TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, P53↑, P21↑, COX2↓, NF-kB↓, Akt↑, NOTCH↓, CDK2↓, CDK6↓, JAK↓, STAT3↓, EGFR↓, p‑ERK↓, p‑Akt↓, p‑STAT3↓, TGF-β↓, SMAD3↓, CDK6↓, Wnt/(β-catenin)↓, Myc↓, survivin↓, CDK8↓, PKCδ↓, tumCV↓, RadioS↑, eff↑, MDM2↓, XIAP↓, p‑RB1↓, PTEN↑, p‑FAK↓, Bax:Bcl2↑, Bcl-xL↓, Mcl-1↓, PUMA↑, NOXA↑, MMP↓, Cyt‑c↑, ROS↑, Ca+2↝, Endoglin↑, Diablo↑, AIF↑, iNOS↓, Casp9↑, Casp3↑, cl‑PARP↑, RadioS↑, Hif1a↓, HO-1↓, HO-2↓, SIRT1↓, selectivity↑, Dose∅, NHE1↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, PDK1?, PDK1?, ECAR↝, COX1↓, Snail↓, Twist↓, cMyc↓, Telomerase↓, angioG↓, MMP2↓, MMP9↓, VEGF↓, Dose↝, PD-L1↓, eff↑, SIRT6↑, DNAdam↓,
1610- EA,    Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer
- Review, Cerv, NA
TumCCA↑, STAT3↓, P21↑, IGFBP7↑, Akt↓, mTOR↓, ROS↑, DNAdam↑, P53↑, P21↑, BAX↑,
1606- EA,    Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells
- in-vitro, Colon, HCT15
TumCP↓, cycD1/CCND1↓, Apoptosis↑, PI3K↓, Akt↓, ROS↑, Casp3↑, Cyt‑c↑, Bcl-2↓, TumCCA↑, Dose∅, ALP↓, LDH↓, PCNA↓, P53↑, Bax:Bcl2↑,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   GSH↓, 1,   HO-1↓, 1,   HO-2↓, 1,   ROS↑, 5,   TBARS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   ECAR↝, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   LDH↓, 1,   PDK1?, 2,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Akt↑, 1,   p‑Akt↓, 1,   Apoptosis↑, 2,   BAX↑, 3,   Bax:Bcl2↑, 3,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 3,   Casp9↑, 1,   Cyt‑c↑, 2,   Diablo↑, 1,   iNOS↓, 1,   Mcl-1↓, 1,   MDM2↓, 1,   Myc↓, 1,   NOXA↑, 1,   PUMA↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   DNAdam↑, 2,   P53↑, 5,   cl‑PARP↑, 1,   PCNA↓, 1,   SIRT6↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 4,   p‑RB1↓, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

CDK8↓, 1,   p‑ERK↓, 1,   IGFBP7↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   PI3K↓, 1,   PTEN↑, 1,   STAT3↓, 2,   p‑STAT3↓, 2,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

Ca+2↝, 1,   p‑FAK↓, 1,   MMP2↓, 1,   MMP9↓, 2,   PKCδ↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCP↓, 2,   Twist↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 1,   Endoglin↑, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

NHE1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 2,   IL6↓, 1,   Inflam↓, 1,   JAK↓, 1,   NF-kB↓, 1,   p‑NF-kB↓, 1,   PD-L1↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 2,  

Drug Metabolism & Resistance ⓘ

Dose↝, 1,   Dose∅, 4,   eff↑, 3,   RadioS↑, 3,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

ALP↓, 1,   EGFR↓, 1,   IL6↓, 1,   LDH↓, 1,   Myc↓, 1,   PD-L1↓, 1,  
Total Targets: 97

Pathway results for Effect on Normal Cells:


Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome
5 Ellagic acid
1 Curcumin
1 Radiotherapy/Radiation
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#:74  Target#:236  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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