Urolithin / Apoptosis 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


Apoptosis, Apoptosis: Click to Expand ⟱
Source:
Type: type of cell death
Situation in which a cell actively pursues a course toward death upon receiving certain stimuli.
Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.


Scientific Papers found: Click to Expand⟱
4835- Uro,    Urolithin A, induces apoptosis and autophagy crosstalk in Oral Squamous Cell Carcinoma via mTOR /AKT/ERK1/2 pathway
- in-vitro, SCC, NA
TumCD↑, ER Stress↑, Akt↓, mtDam↓, p‑mTOR↓, *BioAv↝, ROS↑, TumCCA↑, Apoptosis↑, ERK↓,
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↓,
4841- Uro,    Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells
- in-vitro, CRC, HT29 - in-vitro, CRC, SW480 - in-vitro, CRC, SW-620
TumCP↓, TumCCA↑, Apoptosis↑, P53↑, P21↑, Bcl-2↓, Cyt‑c↑, Casp↑, ROS↑, *ROS↓,
4833- Uro,    Unveiling the potential of Urolithin A in Cancer Therapy: Mechanistic Insights to Future Perspectives of Nanomedicine
- Review, Var, NA - Review, AD, NA - Review, IBD, NA
BioAv↝, TumAuto↝, TumCG↓, TumMeta↓, ChemoSen↑, Imm↑, RadioS↑, BioAv↑, other↝, eff↓, *antiOx↓, *Inflam↓, AntiCan↓, AntiAge↑, chemoP↑, *neuroP↑, *ROS↓, *cognitive↑, *lipid-P↓, *cardioP↑, *TNF-α↓, *IL6↓, GutMicro↑, TumCCA↑, Apoptosis↑, angioG↓, NF-kB↓, PI3K↓, Akt↓, Casp↑, survivin↓, TumCP↓, cycD1/CCND1↓, cMyc↑, BAX↑, Bcl-2↓, COX2↓, P53↑, p38↑, *ROS↓, *SOD↑, *GPx↑, SIRT1↑, FOXO1↑, eff↑, ChemoSen↑,
4846- Uro,    Urolithin A exerts anti-tumor effects on gastric cancer via activating autophagy-Hippo axis and modulating the gut microbiota
- in-vivo, GC, NA
TumCG↓, Hippo↑, Warburg↓, Apoptosis↑, GutMicro↑,
4847- Uro,    Metabolite of ellagitannins, urolithin A induces autophagy and inhibits metastasis in human sw620 colorectal cancer cells
- in-vitro, CRC, SW-620
TumCP↓, TumCMig↓, MMP9↓, TumAuto↑, Apoptosis↑, TumCCA↓, TumMeta↓, ChemoSen↓,
4849- Uro,    Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway
- vitro+vivo, GC, NA
TumCP↓, TumCI↓, TumCMig↓, Apoptosis↑, TumAuto↑, TumCG↓, chemoP↑, ChemoSen↑,
4852- Uro,    Dietary Urolithin B Suppresses Lung Tumorigenesis Correlating with Autophagy Induction and Gut Microbiota Remodeling
- vitro+vivo, Lung, NA
TumCG↓, *GutMicro↑, *Inflam↓, *antiOx↑, AntiTum↑, TumCCA↑, Apoptosis↑,
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↝,
4854- Uro,    Urolithins: Emerging natural compound targeting castration-resistant prostate cancer (CRPC)
- Review, Pca, NA
AR↓, ROS↓, Apoptosis↑, selectivity↑, Dose↑, MDA↓, SOD↑, GPx↑, ROS↑, Casp3↑, Casp9↑,
4856- Uro,    Study on the biological mechanism of urolithin a on nasopharyngeal carcinoma in vitro
- in-vitro, NPC, CNE1 - in-vitro, NPC, CNE2
Apoptosis↑, MMP↓, ROS↑, E-cadherin↑, BAX↑, cl‑Casp3↑, PARP↑, MMP2↓, MMP9↓, N-cadherin↓, Vim↓, Snail↓, eff↓, TumCP↓, TumCMig↓, TumCI↓, EMT↓,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GPx↑, 1,   MDA↓, 1,   ROS↓, 2,   ROS↑, 4,   SOD↑, 1,  

Mitochondria & Bioenergetics

MMP↓, 2,   mtDam↓, 1,  

Core Metabolism/Glycolysis

cMyc↓, 1,   cMyc↑, 1,   SIRT1↑, 1,   Warburg↓, 1,  

Cell Death

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 12,   BAX↑, 2,   Bcl-2↓, 2,   Casp↑, 2,   Casp3↑, 2,   cl‑Casp3↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   Hippo↑, 1,   p38↑, 1,   survivin↓, 1,   TumCD↑, 1,  

Kinase & Signal Transduction

p‑p70S6↓, 1,  

Transcription & Epigenetics

other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

ER Stress↑, 1,  

Autophagy & Lysosomes

TumAuto↑, 3,   TumAuto↝, 1,  

DNA Damage & Repair

P53↑, 3,   PARP↑, 2,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State

EMT↓, 1,   ERK↓, 2,   FOXO1↑, 1,   IGF-1↓, 1,   mTOR↓, 1,   p‑mTOR↓, 1,   PI3K↓, 3,   RAS↓, 1,   TumCG↓, 5,   Wnt↓, 2,  

Migration

E-cadherin↑, 1,   ER-α36↝, 1,   MMP2↓, 1,   MMP9↓, 2,   N-cadherin↓, 1,   Snail↓, 1,   Treg lymp↓, 1,   TumCI↓, 2,   TumCMig↓, 4,   TumCP↓, 8,   TumMeta↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature

angioG↓, 1,   TAMS↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   IL1β↓, 1,   IL6↓, 1,   Imm↑, 1,   NF-kB↓, 2,  

Hormonal & Nuclear Receptors

AR↓, 2,  

Drug Metabolism & Resistance

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 3,   Dose↑, 1,   eff↓, 2,   eff↑, 1,   Half-Life↝, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers

AR↓, 2,   GutMicro↑, 2,   IL6↓, 1,  

Functional Outcomes

AntiAge↑, 1,   AntiCan↓, 1,   AntiCan↑, 1,   AntiTum↑, 1,   chemoP↑, 2,   OS↑, 1,   toxicity↓, 1,  
Total Targets: 88

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↓, 1,   antiOx↑, 1,   GPx↑, 1,   lipid-P↓, 1,   ROS↓, 3,   SOD↑, 1,  

Immune & Inflammatory Signaling

IL6↓, 1,   Inflam↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance

BioAv↑, 2,   BioAv↝, 2,  

Clinical Biomarkers

GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes

cardioP↑, 1,   cognitive↑, 1,   neuroP↑, 1,   toxicity↓, 2,  
Total Targets: 17

Scientific Paper Hit Count for: Apoptosis, Apoptosis
12 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#:14  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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