Urolithin / P21 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


P21, P21: Click to Expand ⟱
Source:
Type: Proapototic
cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli.
P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage.
P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells.
In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein.
Cell cycle arrest gene p21
Scientific Papers found: Click to Expand⟱
4857- Uro,    Evaluation and comparison of the anti-proliferative and anti-metastatic effects of urolithin A and urolithin B against esophageal cancer cells: an in vitro and in silico study
- in-vitro, ESCC, KYSE-30
tumCV↓, selectivity↑, TumCCA↑, ROS↑, Bcl-2↓, BAX↑, P21↑, MMP2↓, MMP9↓,
4845- Uro,    The gut microbiota metabolite urolithin A, but not other relevant urolithins, induces p53-dependent cellular senescence in human colon cancer cells
- in-vitro, Colon, HCT116
TumCCA↑, P53↑, P21↑,
4839- Uro,    Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, LNCaP
tumCV↓, Apoptosis↓, P53↑, P21↑, PUMA↑, NOXA↑, MDM2↓, XIAP↓,
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↓,
4848- Uro,  OXA,    Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells
- in-vitro, Colon, HCT116
TumCG↓, ChemoSen↑, P53↝, P21↑,

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↑, 2,  

Mitochondria & Bioenergetics ⓘ

XIAP↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 2,   Casp↑, 1,   Cyt‑c↑, 1,   MDM2↓, 1,   NOXA↑, 1,   PUMA↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

DNA Damage & Repair ⓘ

P53↑, 3,   P53↝, 1,  

Cell Cycle & Senescence ⓘ

P21↑, 5,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

TumCG↓, 1,  

Migration ⓘ

MMP2↓, 1,   MMP9↓, 1,   TumCP↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   selectivity↑, 1,  
Total Targets: 22

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  
Total Targets: 1

Scientific Paper Hit Count for: P21, P21
5 Urolithin
1 Oxaliplatin
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#:234  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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