ZO-1 Cancer Research Results

ZO-1, Zonula occludens-1: Click to Expand ⟱
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ZO-1 (Zonula occludens-1) is a protein that plays a crucial role in the formation and maintenance of tight junctions in epithelial cells. Tight junctions are essential for maintaining the integrity of epithelial barriers and regulating the passage of ions and molecules across the cell membrane.

In the context of cancer, ZO-1 has been implicated in several ways:

1.Loss of ZO-1 expression: Reduced or lost expression observed in various types of cancer.
2.Disruption of tight junctions: Cancer cells often exhibit disrupted tight junctions, which can lead to increased permeability and the loss of epithelial barrier function. ZO-1 is a key component of tight junctions, and its disruption can contribute to the development and progression of cancer.
3.Epithelial-to-mesenchymal transition (EMT): ZO-1 has been shown to play a role in regulating EMT, a process by which epithelial cells acquire a mesenchymal phenotype. EMT is a key event in the development of cancer metastasis, and ZO-1's role in regulating this process is an area of active research.
4.Tumor suppressor function: ZO-1 has been proposed to have tumor suppressor functions, and its loss or downregulation can contribute to the development of cancer. ZO-1's tumor suppressor functions may be related to its ability to regulate cell growth, apoptosis, and cell migration.

ZO-1 generally acts as a tumor suppressor by maintaining epithelial integrity. In many cancers, downregulation or mislocalization of ZO-1 is observed and is associated with a poorer prognosis due to the facilitation of EMT and metastasis.
Scientific Papers found: Click to Expand⟱
5663- BNL,    Osthole/borneol thermosensitive gel via intranasal administration enhances intracerebral bioavailability to improve cognitive impairment in APP/PS1 transgenic mice
- in-vivo, AD, NA
*ZO-1↓, Mechanisms showed that borneol as a “courier” opened up intercellular space and loosened the tight junctions of the nasal mucosa by suppressing ZO-1 and occludin expression
*cl‑Casp3↓, Osthole assisted by borneol demonstrated significantly improved efficiency in suppressing cleaved caspase-3 expression, increasing the Bcl-2/Bax ratio
*Bax:Bcl2↓,
*MDA↓, reducing malondialdehyde levels, inhibiting neuron apoptosis, and decreasing Aβ levels by inhibiting BACE1 expression to alleviate cognitive impairment in APP/PS1 mice
*Apoptosis↓,
*Aβ↓,
*BACE↓,
*cognitive↑,
*BioAv↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
memory↑, our study demonstrated that the intracerebral bioavailability of osthole profoundly improved with intranasal administration of osthole/borneol
P-gp↓, This may be caused by a higher dose of BO inhibiting the action of the P-gp transporter in intestinal mucosa and CYP450 metabolism in the liver.
BioEnh↑,

6108- Chol,    Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health
- Review, Nor, NA - Review, AD, NA
*TMAO↑, The gut microbiota’s role in metabolizing phytoestrogens suggests that these compounds can modulate the microbial community structure, potentially affecting the production of TMAO from dietary choline and carnitine [5].
*ROS↑, TMAO has the ability to induce oxidative stress in cells by promoting the production of reactive oxygen species (ROS).
*NADPH↑, TMAO has been shown to increase the activity of NADPH oxidase [30], an enzyme that generates ROS as part of its normal function.
*Ca+2↑, TMAO enters platelets and facilitates the release of calcium ions (Ca2+) from intracellular stores.
*AntiAg↓, Calcium serves as a critical secondary messenger in platelet activation, and its elevated levels promote platelet aggregation and thrombus formation
*cognitive↓, TMAO has been linked to cognitive decline and neurodegenerative disorders, including Alzheimer’s disease (AD). Through an integrated analysis of genetic, epigenetic, pathological, and biochemical data, Xu et al. identified a correlation between gut m
*TJ↓, However, excessive TMAO concentrations disrupt BBB integrity by inhibiting tight junction proteins, including claudin-5 and zonula occludens-1
*CLDN1↓,
*ZO-1↓,
*Inflam↑, TMAO also triggers neuroinflammation by activating the NLRP3 inflammasome,
*NLRP3↑,
*ER Stress↑, TMAO enhances the ER stress response by activating the PERK-eIF2α pathway, which is known to impair synaptic plasticity and neuronal function, processes strongly implicated in AD progression
*cognitive↓, TMAO has been identified as the most predictive biomarker for memory impairment and cognitive decline among 56 microbiota-derived metabolic markers
*Dose↝, use of cooking methods such as boiling or stewing instead of grilling, which can produce higher amounts of TMAO
*eff↑, Studies suggest that Lactobacillus plantarum ZDY04 could help reduce TMAO concentrations and prevent TMAO-induced atherosclerosis in animal models
*other↝, Currently, no medications specifically designed to reduce blood TMAO levels exist
*other↝, a review published in 2025 has highlighted the potential role of statins in lowering TMAO levels independently of their cholesterol-lowering effects
*other↝, scientific evidence suggests that statins selectively inhibit the growth of pathogenic bacteria, such as Clostridium and Ruminococcus, while promoting beneficial species, such as Bifidobacterium and Lactobacillus

2952- PL,    Piperlongumine suppresses bladder cancer invasion via inhibiting epithelial mesenchymal transition and F-actin reorganization
- in-vitro, Bladder, T24/HTB-9 - in-vivo, Bladder, NA
TumCP↓, PL significantly suppressed bladder cancer cell proliferation, the transition of G2/M phase to next phase, migration/invasion in vitro and bladder cancer growth/development in vivo
TumCCA↑,
TumCMig↓,
TumCI↓,
ROS↑, PL markedly elevated reactive oxygen species (ROS)
Slug↓, PL inhibited epithelial mesenchymal transition with profoundly decreased level of Slug, β-catenin, ZEB1 and N-Cadherin.
β-catenin/ZEB1↓,
Zeb1↓,
N-cadherin↓,
F-actin↓, decreased F-actin intensity in bladder cancer cells
GSH↓, Consistently, intracellular glutathione (GSH) levels were significantly reduced in T24 cells at 3 h of PL treatment
EMT↓, PL inhibited epithelial mesenchymal transition
CLDN1↓, The decline of Claudin-1 and ZO-1 upon PL treatment
ZO-1↓,

3025- RosA,    Rosmarinic acid alleviates intestinal inflammatory damage and inhibits endoplasmic reticulum stress and smooth muscle contraction abnormalities in intestinal tissues by regulating gut microbiota
- in-vivo, IBD, NA
*GutMicro↑, RA upregulated the abundance of Lactobacillus johnsonii and Candidatus Arthromitus sp SFB-mouse-NL and downregulated the abundance of Bifidobacterium pseudolongum, Escherichia coli, and Romboutsia ilealis.
*ROCK1↓, RA downregulated the expressions of ROCK, RhoA, CaM, MLC, MLCK, ZEB1, ZO-1, ZO-2, occludin, E-cadherin, IL-1β, IL-6, TNF-α, GRP78, PERK, IRE1, ATF6, CHOP, Caspase12, Caspase9, Caspase3, Bax, Cytc, RIPK1, RIPK3, MLKL
*Rho↓,
*CaMKII ↓,
*Zeb1↓,
*ZO-1↓,
*E-cadherin↓,
*IL1β↓,
*IL6↓,
*TNF-α↓,
*GRP78/BiP↓,
*PERK↓,
*IRE1↓,
*ATF6↓,
*CHOP↓,
*Casp12↓,
*Casp9↓,
*BAX↓,
*Casp3↓,
*Cyt‑c↓,
*RIP1↓,
*MLKL↓,
*IL10↑, upregulated the expression of IL-10 and Bcl-2.
*Bcl-2↑,
*ER Stress↓, RA inhibited the inflammation, which is caused by tight junction damage, by repairing intestinal flora dysbiosis, relieved endoplasmic reticulum stress, inhibited cell death


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   ROS↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,  

Migration ⓘ

CLDN1↓, 1,   F-actin↓, 1,   N-cadherin↓, 1,   Slug↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   Zeb1↓, 1,   ZO-1↓, 1,   β-catenin/ZEB1↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh↑, 1,  

Functional Outcomes ⓘ

memory↑, 1,  
Total Targets: 17

Pathway results for Effect on Normal Cells:


NA, unassigned ⓘ

TMAO↑, 1,  

Redox & Oxidative Stress ⓘ

MDA↓, 1,   ROS↑, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↑, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Casp12↓, 1,   Casp3↓, 1,   cl‑Casp3↓, 1,   Casp9↓, 1,   Cyt‑c↓, 1,   MLKL↓, 1,   RIP1↓, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 3,  

Protein Folding & ER Stress ⓘ

ATF6↓, 1,   CHOP↓, 1,   ER Stress↓, 1,   ER Stress↑, 1,   GRP78/BiP↓, 1,   IRE1↓, 1,   PERK↓, 1,  

Migration ⓘ

AntiAg↓, 1,   Ca+2↑, 1,   CLDN1↓, 1,   E-cadherin↓, 1,   Rho↓, 1,   ROCK1↓, 1,   TJ↓, 1,   Zeb1↓, 1,   ZO-1↓, 3,  

Immune & Inflammatory Signaling ⓘ

IL10↑, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↑, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   BACE↓, 1,   NLRP3↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   Dose↝, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

GutMicro↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↓, 2,   cognitive↑, 1,  
Total Targets: 48

Scientific Paper Hit Count for: ZO-1, Zonula occludens-1
1 borneol
1 Choline
1 Piperlongumine
1 Rosmarinic acid
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

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