Urolithin / MIP‑1α/CCL3 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


MIP‑1α/CCL3, C-C Motif Chemokine Ligand 3: Click to Expand ⟱
Source:
Type:
CCL3 (Macrophage Inflammatory Protein-1α, MIP‑1α)

-CCL3 acts as a chemoattractant for various immune cells including NK cells, dendritic cells, and monocytes.

– Its role in tumors can be dual: promoting anti-tumor responses in some contexts while in others, especially through chronic inflammation, it may participate in tumor progression.

CCL3 - C-C Motif Chemokine Ligand 3

Abbreviation: CCL3, MIP-1α

Type: Chemokine / inflammatory cytokine

Function: CCL3 is a CC-family chemokine that signals primarily through CCR1 and CCR5 and regulates recruitment and activation of monocytes, macrophages, lymphocytes, and other immune cells. It plays important roles in inflammatory responses, immune-cell trafficking, and tumor-microenvironment signaling.

Cancer: ↕ Context-dependent. CCL3 can support antitumor immune-cell recruitment in some settings, but elevated CCL3 frequently promotes a pro-inflammatory tumor microenvironment, recruitment of tumor-supportive myeloid cells, angiogenesis, invasion, metastasis, and treatment resistance.

Alzheimer's Disease: ↑ Increased CCL3 is associated with neuroinflammation and activation or recruitment of microglia and other immune cells in Alzheimer's disease and related neurodegenerative models.
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/CCL2↓, *MIP‑1α/CCL3↓, *TNF-α↓, *IL2↓, *SIRT1↓, *DNAdam↓, *Dose↝, *Strength↑, *motorD↑, *CTSZ↓,

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:


Core Metabolism/Glycolysis(tgid=4) ⓘ

SIRT1↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CTSZ↓, 1,   IL1α↓, 1,   IL2↓, 1,   MCP1/CCL2↓, 1,   MIP‑1α/CCL3↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

p‑tau↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   eff↓, 1,  

Functional Outcomes(tgid=23) ⓘ

memory↑, 1,   motorD↑, 1,   Strength↑, 1,   toxicity↓, 1,  
Total Targets: 17

Scientific Paper Hit Count for: MIP‑1α/CCL3, C-C Motif Chemokine Ligand 3
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#:1275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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