Urolithin / toxicity Cancer Research Results

Uro, Urolithin: Click to Expand ⟱
Features:
Urolithins are gut microbiota–derived dibenzopyran-6-one metabolites formed from ellagitannins → ellagic acid. They are the bioactive, systemically relevant forms responsible for most of the anticancer, mitochondrial, and signaling effects attributed to pomegranate and berry consumption.
Ellagic acid itself is largely confined to the gut lumen; urolithins are what reach circulation and tissues.

Urolithin A (UA), Most studied; mitophagy, anticancer, anti-inflammatory
Humans fall into urolithin metabotypes:
Metabotype	Description	            Approx. Population
A	        Produces UA (best profile)	~40%
B	        Produces UB ± UA	       ~25–30%
0	        Non-producer	                ~30%

ROS Modulation (Context-Dependent)
Cancer cells:
-Mild ROS ↑ or redox stress → apoptosis, growth arrest
Normal cells:
-ROS ↓, improved mitochondrial efficiency

This duality is why urolithins are less chemo-antagonistic than classic antioxidants.

Anticancer Signaling
↓ PI3K/AKT/mTOR
↓ Wnt/β-catenin
↓ NF-κB, STAT3
Cell-cycle arrest (G1/S)

Unlike sulforaphane or NAC, urolithins:
-Do not strongly upregulate NRF2 in cancer cells
-May normalize NRF2 signaling in normal cells
Direct Urolithin A Supplements: Bypass microbiome dependency

Urolithin A–type activity — Cancer vs Normal Cell Effects
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Mitophagy / mitochondrial quality control (PINK1–Parkin axis) ↑ mitophagy → loss of mitochondrial reserve ↑ mitophagy → improved mitochondrial fitness Driver Mitochondrial pruning and quality enforcement Urolithins selectively stress cancer cells by removing dysfunctional mitochondria while rejuvenating normal-cell mitochondrial pools
2 Mitochondrial metabolism / bioenergetics ↓ metabolic flexibility; ↓ ATP resilience ↑ oxidative efficiency Driver Energy stress vs optimization Cancer cells are less able to compensate for enforced mitochondrial turnover
3 Reactive oxygen species (ROS) ↑ ROS (secondary to mitochondrial stress) ↓ ROS Secondary Metabolism-linked redox shift ROS changes arise from altered mitochondrial populations, not direct redox cycling
4 AMPK / mTOR nutrient-sensing axis ↑ AMPK; ↓ mTOR signaling ↑ AMPK (adaptive) Secondary Catabolic pressure and growth restraint Energy-sensing pathways reinforce growth suppression in metabolically stressed tumor cells
5 Cell cycle regulation ↓ proliferation / ↑ arrest ↔ spared Phenotypic Cytostatic growth limitation Growth inhibition reflects bioenergetic insufficiency rather than direct CDK inhibition
6 Inflammatory signaling (NF-κB / cytokines) ↓ pro-tumor inflammation ↓ inflammatory tone Secondary Anti-inflammatory modulation Reduced inflammation contributes to chemopreventive and microenvironmental effects
7 NRF2 antioxidant response ↑ NRF2 (adaptive, secondary) ↑ NRF2 (protective) Adaptive Redox homeostasis reinforcement NRF2 activation reflects improved mitochondrial quality and reduced oxidative burden rather than a cytotoxic mechanism
8 Apoptosis sensitivity ↑ sensitivity to apoptosis (stress-context dependent) ↓ apoptosis Phenotypic Threshold-dependent cell death Apoptosis occurs when mitochondrial and energetic stress exceed adaptive capacity


toxicity, toxicity: Click to Expand ⟱
Source:
Type:
Toxicity
Scientific Papers found: Click to Expand⟱
4861- Uro,    Urolithin A improves Alzheimer's disease cognition and restores mitophagy and lysosomal functions
- in-vivo, AD, NA
*memory↑, *Aβ↓, *toxicity↓, *BBB↑, *p‑tau↓, *eff↓, *IL1α↓, *MCP1↓, *MIP‑1α↓, *TNF-α↓, *IL2↓, *SIRT1↓, *DNAdam↓, *Dose↝, *Strength↑, *motorD↑, *CTSZ↓,
4864- Uro,    Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer's Disease
- Review, AD, NA
*neuroP↑, *Half-Life↝, *BBB↑, *toxicity↓, *Inflam↓, *Strength↑, *BACE↓, *Aβ↓, *MitoP↑, *SIRT1↑, *SIRT3↑, *AMPK↑, *PGC-1α↑, *mTOR↓, *PARK2↑, *Beclin-1↑, *ROS↓, *GutMicro↑, *Risk↓,
4837- Uro,    Urolithins: The Gut Based Polyphenol Metabolites of Ellagitannins in Cancer Prevention, a Review
- Review, Var, NA
AntiCan↑, TumCCA↑, Apoptosis↑, TumAuto↑, *BioAv↝, *BioAv↑, RAS↓, ERK↓, AR↓, TumCP↓, PI3K↓, Akt↓, NF-kB↓, COX2↓, IL6↓, IL1β↓, Wnt↓, β-catenin/ZEB1↓, cMyc↓, P53↑, Casp3↑, PARP↑, ROS↓, toxicity↓,
4840- Uro,    Urolithin A: A promising selective estrogen receptor modulator and 27-hydroxycholesterol attenuator in breast cancer
- vitro+vivo, BC, NA
MMP↓, TumCP↓, Apoptosis↑, tumCV↓, ER-α36↝, *toxicity↓,
4853- Uro,    Urolithin A, a novel natural compound to target PI3K/AKT/mTOR pathway in pancreatic cancer
- vitro+vivo, PC, MIA PaCa-2 - in-vitro, NA, PANC1
p‑Akt↓, p‑p70S6↓, TumCG↓, OS↑, PI3K↓, mTOR↓, TumCP↓, TumCMig↓, Apoptosis↑, TAMS↓, Treg lymp↓, Wnt↓, IGF-1↓, *toxicity↓, *BioAv↑, Half-Life↝,

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 ⓘ

ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 3,   Casp3↑, 1,  

Kinase & Signal Transduction ⓘ

p‑p70S6↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   PARP↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   IGF-1↓, 1,   mTOR↓, 1,   PI3K↓, 2,   RAS↓, 1,   TumCG↓, 1,   Wnt↓, 2,  

Migration ⓘ

ER-α36↝, 1,   Treg lymp↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

TAMS↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL6↓, 1,   NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

Half-Life↝, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   OS↑, 1,   toxicity↓, 1,  
Total Targets: 37

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

PARK2↑, 1,   ROS↓, 1,   SIRT3↑, 1,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   SIRT1↓, 1,   SIRT1↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   MitoP↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

mTOR↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

CTSZ↓, 1,   IL1α↓, 1,   IL2↓, 1,   Inflam↓, 1,   MCP1↓, 1,   MIP‑1α↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 2,   BioAv↝, 1,   Dose↝, 1,   eff↓, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,  

Functional Outcomes ⓘ

memory↑, 1,   motorD↑, 1,   neuroP↑, 1,   Risk↓, 1,   Strength↑, 2,   toxicity↓, 4,  
Total Targets: 34

Scientific Paper Hit Count for: toxicity, toxicity
5 Urolithin
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#:383  Target#:1025  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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