Urolithin / FIS1 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


FIS1, Mitochondrial fission 1 protein: Click to Expand ⟱
Source:
Type:

FIS1 — Mitochondrial fission 1 protein
FIS1 is a mitochondrial outer-membrane fission adaptor/receptor linked to DRP1-mediated mitochondrial dynamics. In cancer, FIS1 is an emerging target because mitochondrial fission supports proliferation, survival adaptation, metastatic behavior, and tumor-initiating/stem-like phenotypes in some models. Recent TNBC evidence suggests FIS1 is required for expansion of tumor-initiating cells and that FIS1 loss suppresses TIC activity without broadly collapsing mitochondrial function, making it a potentially more selective mitochondrial dynamics target than global DRP1 inhibition.

-Often pro-tumor, Supports mitochondrial fragmentation/dynamics in stress-adapted cells

FIS1 is relevant to Alzheimer’s disease as part of the pathological mitochondrial fission program. AD models and human tissue studies show an imbalance toward mitochondrial fission, involving increased DRP1 and FIS1 and reduced fusion proteins such as MFN1, MFN2, and OPA1. Aβ and phosphorylated tau are linked to abnormal DRP1-mediated mitochondrial fragmentation, and increased DRP1/FIS1 interaction has been reported in Aβ-treated neurons and AD patient-derived fibroblasts.
-Direction: Usually increased or overactive in AD-like pathology

Natural Product Reported FIS1 / Fission Effect Evidence Strength for FIS1 Cancer Relevance Database Classification Suggested Note
Curcumin Reported to decrease FIS1 and DRP1-associated mitochondrial fission in several mitochondrial injury models. Moderate to strong Indirect; FIS1-specific cancer evidence is limited. FIS1/DRP1 mitochondrial fission down-modulator Best-supported natural product to link with FIS1, but still mostly non-cancer evidence.
EGCG Reported to decrease FIS1 or regulate the DRP1/FIS1 mitochondrial dynamics axis in neuroprotection and injury models. Moderate Indirect; stronger evidence for mitochondrial quality control than cancer-specific FIS1 targeting. Possible FIS1 down-modulator Useful to tag under mitochondrial fission, mitophagy, and oxidative-stress adaptation.
Urolithin A Reported to decrease FIS1 and DRP1 while improving mitophagy and mitochondrial quality control. Moderate Indirect; mostly neurodegeneration/mitophagy evidence. FIS1/DRP1-associated mitochondrial quality-control modulator Better classified under mitophagy and mitochondrial quality control
Melatonin Often reported to reduce pathological DRP1/FIS1-mediated mitochondrial fission, but effects can be context-dependent. Moderate Indirect; cancer relevance is complex and context-dependent. Context-dependent mitochondrial dynamics modulator “normalizes mitochondrial dynamics” rather than simple FIS1 inhibition.
Resveratrol Can reduce pathological DRP1/FIS1 fission in some injury models, but may increase Fis1/Drp1 expression in aging-repair contexts. Mixed Indirect; direction may vary by model and dose. Context-dependent FIS1/DRP1 modulator not a simple FIS1 inhibitor; more a mitochondrial dynamics normalizer.
Quercetin Associated with FIS1 targeting in omics/computational studies; direct experimental FIS1 modulation is weaker. Weak to moderate Indirect; not validated as a FIS1-targeted anticancer compound. Putative FIS1-associated modulator Suitable as a low-confidence or “possible” FIS1 link.
Sulforaphane Inhibits mitochondrial fission mainly through DRP1-related mechanisms; direct FIS1 modulation is unclear. Weak for FIS1 specifically Indirect; relevant to cancer metabolism and oxidative stress, but not FIS1-specific. Broader DRP1/fission pathway modulator mitochondrial fission rather than direct FIS1 modulation.
Berberine Reported to inhibit DRP1-mediated mitochondrial fission; FIS1 is mainly implicated as part of the pathway rather than directly modulated. Weak for FIS1 specifically Indirect; potentially relevant to cancer metabolism but not validated through FIS1. Broader DRP1/fission pathway modulator not a direct FIS1 modulator unless using a broader mitochondrial fission category.


Scientific Papers found: Click to Expand⟱
6412- Uro,  EGCG,    A Combination Therapy of Urolithin A+EGCG Has Stronger Protective Effects than Single Drug Urolithin A in a Humanized Amyloid Beta Knockin Mice for Late-Onset Alzheimer’s Disease
- in-vivo, AD, NA
*Aβ↓, *eff↑, *cognitive↑, *neuroG↑, *BBB↑, *TNF-α↓, *IL1β↓, *IL6↓, *p‑tau↓, *FIS1↓, *ATP↑, *lipid-P↓,

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:


NA, unassigned ⓘ

FIS1↓, 1,  

Redox & Oxidative Stress ⓘ

lipid-P↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

neuroG↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

p‑tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,  
Total Targets: 13

Scientific Paper Hit Count for: FIS1, Mitochondrial fission 1 protein
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#:1486  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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