ZO-1 Cancer Research Results

ZO-1, Zonula occludens-1: Click to Expand ⟱

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Type:

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⟱

5365-

AV,

Aloe Vera Polysaccharides as Therapeutic Agents: Benefits Versus Side Effects in Biomedical Applications

Review,

Nor,

Review,

IBD,

Review,

Diabetic,

*Wound Healing↑, Traditionally recognized for its anti-inflammatory and antimicrobial effects, which are very important in wound healing, the Aloe Vera relies on its polysaccharides
*Imm↑, which confer immunomodulatory, antioxidant, and tissue-regenerative properties.
*antiOx↑,
*AntiDiabetic↑, graphical abstract
*AntiCan↑,
*Inflam↓, The anti-inflammatory properties of Aloe Vera polysaccharides are primarily mediated through the inhibition of key inflammatory pathways.
*NF-kB↓, Acemannan and other polysaccharides suppress the activation of nuclear factor-kappa B (NF-κB), a transcription factor that regulates the expression of pro-inflammatory genes.
*COX2/PTGS2↓, By inhibiting NF-κB [48,49], Aloe Vera polysaccharides reduce the production of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX),
*5LO↓,
*IL1β↓, Aloe Vera polysaccharides downregulate the expression of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, while upregulating anti-inflammatory cytokines such as IL-10
*IL6↓,
*TNF-α↓,
*IL10↑,
*other↓, This dual action helps to mitigate inflammation in conditions such as arthritis, dermatitis, and inflammatory bowel disease (IBD)
*ROS↓, Aloe Vera polysaccharides exhibit potent antioxidant activity by scavenging reactive oxygen species (ROS) and free radicals,
*SOD↑, The polysaccharides enhance the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), which neutralize oxidative stress and protect cells from damage [17,63].
*Catalase↑,
*GPx↑,
*lipid-P↓, This property is particularly beneficial in preventing lipid peroxidation, DNA damage, and protein oxidation, processes associated with chronic diseases and aging
*DNAdam↓,
*GutMicro↑, Aloe Vera polysaccharides support gastrointestinal health, acting as prebiotics and promoting the growth of beneficial gut microbiota such as Lactobacillus and Bifidobacterium species [64].
*ZO-1↑, enhance the integrity of the intestinal epithelial barrier by upregulating the expression of tight junction proteins such as occludin and zonula occludens-1 (ZO-1) [51,54].
AntiTum↑, Certain polysaccharides in Aloe Vera, including acemannan, have demonstrated antitumoral effects by inducing apoptosis (programmed cell death) in cancer cells.
Casp3↑, This is achieved through the activation of caspase-3 and caspase-9, key enzymes in the apoptotic pathway [45,48].
Casp9↑,
angioG↓, Aloe Vera polysaccharides also inhibit angiogenesis and metastasis by downregulating matrix metalloproteinases (MMPs) and VEGF [75].
MMPs↓,
VEGF↓,
NK cell↑, Moreover, these polysaccharides enhance the immune system’s ability to recognize and destroy cancer cells through stimulating natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) [43,55].

1098-

BA,

Baicalein inhibits fibronectin-induced epithelial–mesenchymal transition by decreasing activation and upregulation of calpain-2

in-vitro,

Nor,

MCF10

in-vivo,

NA,

mouse

*TumCMig↓,
*F-actin↓,
*E-cadherin↑,
*ZO-1↑,
*N-cadherin↓,
*Vim↓,
*Snail↓,
*cal2↓, baicalein inhibited calpain-2 by decreasing intracellular calcium ion levels
*Ca+2↝, Effects of baicalein on fibronectin (FN)-induced intracellular elevation of Ca2+ Returns elevated levels close to back to original levels.

2617-

Ba,

Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review

Review,

Var,

Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2/KDR/Flk1↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

5740-

Buty,

A Review of Nutritional Regulation of Intestinal Butyrate Synthesis: Interactions Between Dietary Polysaccharides and Proteins

Review,

RCC,

*eff↓, excessive protein fermentation produces branched-chain fatty acid (BCFA), ammonia, phenols, and other metabolites that inhibit butyrate production
Dose↝, Several studies have found that the ratio of acetate to propionate to butyrate in the colon of healthy individuals (regardless of region) has been found to be approximately 60:20:20 [2,3].
eff↑, An appropriate polysaccharide-to-protein ratio appears crucial for maintaining gut microbial homeostasis and facilitating butyrate generation.
HDAC↓, butyrate is a classic HDAC inhibitor that increases the acetylation level of histone H3 and H4,
ac‑H3↓,
ac‑H4↓,
*HCAR2↑, butyrate is produced by the gut microbiota at high concentrations (10–20 mM) and acts as an endogenous agonist of GPR109A.
*Inflam↓, When butyrate activates GPR109A on colonocytes, it triggers intracellular signaling cascades, promotes the secretion of the anti-inflammatory cytokine IL-18,
*ROS↓, Moreover, butyrate reduces the level of reactive oxygen species by activating the Nrf2 antioxidant pathway and enhancing glutathione (GSH) synthesis, and alleviate stress damage to the to intestinal barrier and immune cells.
*NRF2↑,
*GSH↑,
*CLDN1↑, Butyrate also enhances epithelial barrier function by upregulating the expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1 in intestinal epithelial cells.
*ZO-1↑,
IL1β↓, rucial role in repairing and strengthening the intestinal barrier by downregulating the transcription of pro-inflammatory genes, including IL-1β, IL-6, and COX-2,
IL6↓,
COX2/PTGS2↓,
eff↝, Different types of monosaccharides significantly influence the efficiency of butyrate production due to their distinct chemical properties and microbial utilization mechanisms.
eff↑, After entering the colon, polysaccharides serve as fermentation substrates for gut microbiota and are broken down into butyrate.
other↝, A central challenge in current research on gut microbiota and butyrate production lies in determining the optimal dietary ratio of polysaccharides to proteins.

5932-

CAR,

Carvacrol attenuates mucosal barrier impairment and tumorigenesis by regulating gut microbiome

in-vivo,

IBD,

Male C57BL/6 J mice

in-vivo,

Park,

*GutMicro↑, Carvacrol can regulate the gut microbiota. bundance of specific microbiota, such as Lactobacillus, Escherichia coli/Shigella, and Lachnoclostridium.
Risk↓, Carvacrol inhibits the development of colitis-associated colorectal cancer.
*Inflam↓, nti-inflammatory and antioxidant traits,
*antiOx↓,
*ZO-1↑, carvacrol significantly restored colonic length (p < 0.01) and re-established key tight junction proteins like ZO-1.
*iNOS↓, downregulated mRNA levels of inflammatory mediators such as iNOS and IL-6.
*IL6↓,
*NO↓, carvacrol has been shown to suppress nitric oxide and prostaglandin E2 production
*PGE2↓,
*memory↑, carvacrol improves memory deficits in Parkinson’s disease models
*TLR4↓, anti-inflammatory effects of carvacrol by inhibiting the TLR4/NF-κB signaling pathway
*NF-kB↓,
*IBI↑, Carvacrol improves intestinal barrier function
*CLDN3↑, expression levels of ZO-1, Claudin3, Claudin1, Occludin, and Mucin were significantly increased in the carvacrol group compared to the DSS group
*CLDN1↑,
*MUC1↑,
*OCLN↑,
*iNOS↑, carvacrol significantly inhibited the mRNA expression levels of iNOS, COX-2, Interferon-γ, IL-1β, and IL-6 in the intestinal tracts of colitis mice
*COX2/PTGS2↓,
*IFN-γ↓,
IL1β↓,
ADAM10?,

1106-

CGA,

Chlorogenic Acid Inhibits Epithelial-Mesenchymal Transition and Invasion of Breast Cancer by Down-Regulating LRP6

vitro+vivo,

BC,

MCF7

E-cadherin↑,
ZO-1↑,
Zeb1↓,
N-cadherin↓,
Vim↓,
Snail↓,
Slug↓,
MMP2↓,
MMP9↓,
TumCMig↓,
TumCI↓,
LRP6↓,
p‑LRP6↓,
β-catenin/ZEB1↓,
TumVol↓, in vivo
TumW↓,

429-

CUR,

TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression

in-vitro,

Lung,

H1299

2.5, 5 and 7.5 μM, 48 h

in-vitro,

Lung,

A549

TAp63α↑,
E-cadherin↑,
ZO-1↑,
Vim↓,
N-cadherin↓,
miR-19b↓, miR-19a, miR-19b

1113-

FIS,

Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

TumCI↓,
TumCMig↓,
EMT↓,
E-cadherin↑, A549
ZO-1↑, h1299
Vim↓,
N-cadherin↓,
MMP2↓,
CD44↓,
CD133↓,
β-catenin/ZEB1↓,
NF-kB↓,
EGFR↓,
STAT3↓,
CSCs↓, ability of fisetin to serve as a potential therapeutic agent on its capacity to attenuate the EMT program and inhibit migration, invasion and stem cell phenotype of lung cancer cells.

7006-

Fuc,

Seaweeds in the Oncology Arena: Anti-Cancer Potential of Fucoidan as a Drug—A Review

Review,

Var,

*toxicity↓, Fucoidan is a versatile, nontoxic marine-origin heteropolysaccharide that has received much attention due to its beneficial biological properties and safety.
*AntiViral↑, ucoidan has been demonstrated to exhibit a variety of conventional bioactivities, such as antiviral, antioxidant, and immune-modulatory characteristics, and anticancer activity against a wide range of malignancies has also recently been discovered.
*antiOx↑,
*Imm⇅,
AntiCan↑,
TumCCA↑, Fucoidan inhibits tumorigenesis by prompting cell cycle arrest and apoptosis, blocking metastasis and angiogenesis, and modulating physiological signaling molecules.
Apoptosis↑,
TumMeta↓,
angioG↓,
antiNeop↑, Fucoidans’ capacity to bind to Toll-like receptors and intervene with the action of vascular endothelial growth factors (VEGF) and matrix metalloproteinases (MMPs) could explain their anti-neoplastic properties
VEGF↓,
MMPs↓,
BioAv↑, Low molecular weight fractions (LMWF), in particular, are thought to be more biocompatible [47]
BioAv↑, in rats, following topical administration of fucoidan (MW 750 kDa) from Fucus vesiculosus demonstrated fine skin-penetrating characteristics.
ROS⇅, Induction/inhibition of reactive oxygen species (ROS), mitochondrial instability, and caspase and poly (ADP-ribose) polymerase (PARP) cleavage are all aspects of it
cl‑PARP↑, fucoidan treatment causes PARP cleavage and caspase-3/7 activation in MCF-7 cells, which are hallmarks of apoptosis [
Casp3↑,
Casp7↑,
ROS↑, human hepatoma SMMC-7721 cells, fucoidan therapy caused noteworthy growth inhibition and ROS-mediated apoptosi
GSH↓, lower glutathione consumption (GSH), mitochondrial swelling, and depolarization of the mitochondrial membrane potential
MMP↓,
PI3K↓, Fucoidan inhibits PI3K, suppressing ERK and activates MAPK, limiting cancer cell proliferation and decreasing Bcl-2 to Bax ratio, inducing caspase-dependent apoptosis in BEL-7402 and LM3 cell lines
ERK↓,
MAPK↑,
TumCP↓,
Bax:Bcl2↑,
TJ↑, Meanwhile, dietary fucoidan progressively restores intestinal villi by upregulating the expression of tight junction proteins such as ZO-1, Occludin, Claudin-1, and Claudin-8 via p38 MAPK and ERK1/2 activation.
ZO-1↑,
OCLN↑,
CLDN1↑,
IBI↑, fucoidan supplementation improves intestinal barrier function by enhancing intestinal microbiota diversity
GutMicro↑,
NK cell↑, ↑NK cell-mediated anticancer immunity
STAT3↓, Inhibits STAT3 Signaling
eff↑, Astragalus polysaccharide as a topical mucosal adjuvant to boost the anticancer efficacy of immune checkpoint inhibitors

1118-

GSE,

Grape Seed Proanthocyanidins Inhibit Migration and Invasion of Bladder Cancer Cells by Reversing EMT through Suppression of TGF- β Signaling Pathway

in-vitro,

Bladder,

T24/HTB-9

in-vitro,

Bladder,

5637

TumCMig↓,
TumCI↓,
MMP2↓,
MMP9↓,
EMT↓,
N-cadherin↓,
Vim↓,
Slug↓,
E-cadherin↑,
ZO-1↑,
p‑SMAD2↓,
p‑SMAD3↓,
p‑Akt↓,
p‑ERK↓,
p‑p38↓,

7928-

H2,

Molecular hydrogen alleviates asthma through inhibiting IL-33/ILC2 axis

in-vivo,

Asthma,

 OVA sensitized asthma mouse model

*IL33↓, Serum and BALF levels of IL-33 and other alarmin and type II cytokines were greatly increased by OVA and inhibited by H2 in asthmatic mice.
*NF-kB↓, The expression of NF-κB (p65) and ST2 was upregulated by OVA and suppressed by H2.
*IL1RL1/ST2↓,
*ILC2↓, ILC2 population was markedly increased in OVA-induced asthmatic mice, and such increase was inhibited by H2.
*E-cadherin↑, E-cadherin and ZO-1 levels in airway tissues of asthmatic mice were significantly lower than that of control mice, and the reduction was recovered by H2 treatment.
*ZO-1↑,
*Inflam↓, These data demonstrated that H2 is efficient in suppressing allergen-induced asthma and could be developed as a therapeutics for asthma and other conditions of type II inflammation.

7560-

HYP,

Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity

Review,

Nor,

Review,

AD,

*RenoP↓, Thirdly, long-term use of hyperoside is toxic to the kidneys, but the damage is reversible
Casp3↑, Up-regulates caspase-3, caspase-8, Bax, p53 and MDA contents; decreases GSH, SOD and CAT activities; decreases VEGF and Bcl-2 levels; and inhibits cell growth. HeLa 100 μmol/L
Casp8↑,
MDA↑,
GSH↓,
SOD↓,
Catalase↓,
VEGF↓,
Bcl-2↓,
TumCG↓,
p‑Akt↓, Down-regulates BMP-7 expression, AKT phosphorylation and PI3K expression; induces cell cycle arrest; and inhibits cell proliferation. Human HepG2 5, 10, 20, 40 and 80 μM
PI3K↓,
TumCCA↑,
TumCP↓,
BMP7/OP1↓,
*ZO-1↑, up-regulates ZO-1 and claudin5 protein expression; maintains the integrity of the blood–brain barrier; and may protect neural function in CIR-injured mice. CIR injury induced by MCAO in mice 50 mg/kg
*BBB↝,
*p‑Akt↑, increases the phosphorylation of AKT and GSK-3β; alleviates early brain injury after subarachnoid haemorrhage; and promotes nerve function recovery in rats.
*GSK‐3β↑,
*SOD↑, increases SOD and CAT activities and GSH content; increases SIRT1 gene expression; down-regulates NF-κB mRNA
*Catalase↑,
*GSH↑,
*SIRT1↑,
*NF-kB↓,
*IL1β↓, Down-regulates IL-1β, IL-6, IL-8, TNF-α, ROS, MDA, Bax and caspase-3 levels; increases CAT, SOD and GSH activities; up-regulates Bcl-2, BDNF, TrkB, SIRT1 and NGF expression; reduces LPS-induced inflammation, oxidative stress and apoptosis; and protec
*IL6↓,
*IL8↓,
*TNF-α↓,
*ROS↓,
*MDA↓,
*BAX↓,
*Casp3↓,
*Bcl-2↑,
*BDNF↑,
*TrkB↑,
*NGF↑,
*Apoptosis↓,
*cardioP↑, Cardioprotective Activity of Hyperoside.
*AST↓, Decreases the levels of AST, CK, CK-MB and c-TnT in rats; the rate of cardiomyocyte apoptosis;
*hepatoP↑, Hepatoprotective Activity of Hyperoside.
*AST↓, Decreases liver index, AST, ALT, MDA and Bach1 complex levels and alleviates the pathological damage of acute liver injury mice.
*ALAT↓,
*MDA↓,
*BACH1↓,
*neuroP↑, Brain-Protective Activity of Hyperoside.
*Stroke↓, Down-regulates TNF-α, IL-1β, IL-6, ICAM-1, VCAM-1, TLR4, COX-2, NF-κB, caspase-3, caspase-9, Bax and Bcl-2 expression and prevents CIR injury. Middle cerebral artery occlusion/reperfusion rat model
*ICAM-1↓,
*VCAM-1↓,
*TLR4↓,
*COX2/PTGS2↓,
*RenoP↑, Renal-Protective Activity of Hyperoside.
*NLRP3↓, Suppresses NLRP3, caspase-1 and ASC expression and prevents acute kidney injury induced by lipopolysaccharide. Mouse acute kidney injury model
*Casp1↓,
*ASC↓,
*BioAv↓, low oral bioavailability
*BioAv↑, hyperoside is compatible with other traditional Chinese medicines and they can improve its bioavailability and oral absorption.
*toxicity↓, Firstly, an acute toxicity test of hyperoside showed that its LD50 > 5000 mg/kg

7861-

isoO,

Isoorientin Inhibits Inflammation in Macrophages and Endotoxemia Mice by Regulating Glycogen Synthase Kinase 3 β

vitro+vivo,

Nor,

RAW264.7

Mice

*Inflam↓, Isoorientin has anti-inflammatory effects; however, the mechanism remains unclear.
*GSK‐3β↓, isoorientin is an inhibitor of glycogen synthase kinase 3β (GSK3β) in vitro
*TNF-α↓, isoorientin decreased the production of TNF-α, IL-6, and IL-1β and increased the expression of p-GSK3β in vitro and in vivo, similar to LiCl.
*IL6↓,
*IL1β↓,
*p‑GSK‐3β↑,
*eff↑, Coadministration of isoorientin and LiCl showed antagonistic effects
*COX2/PTGS2↓, Isoorientin decreased the expression of COX-2, inhibited the activation of ERK and NF-κB, and increased the activation of Nrf2/HO-1 in LPS-induced RAW264.7 cells
*ERK↓,
*NF-kB↓,
*NRF2↑,
*HO-1↑,
*OCLN↑, Isoorientin increased the expressions of occludin and ZO-1 in the brain of endotoxemia mice.
*ZO-1↑,
*BBB↝, protect the integrity of the blood-brain barrier and the homeostasis in the brain.

2921-

LT,

Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies

Review,

Nor,

*hepatoP↑, Due to its excellent liver protective effect, luteolin is an attractive molecule for the development of highly promising liver protective drugs.
*AMPK↑, fig2
*SIRT1↑,
*ROS↓,
STAT3↓,
TNF-α↓,
NF-kB↓,
*IL2↓,
*IFN-γ↓,
*GSH↑,
*SREBP1/SREBF1↓,
*ZO-1↑,
*TLR4↓,
BAX↑, anti cancer
Bcl-2↓,
XIAP↓,
Fas↑,
Casp8↑,
Beclin-1↑,
*TXNIP↓, luteolin inhibited TXNIP, caspase-1, interleukin-1β (IL-1β) and IL-18 to prevent the activation of NLRP3 inflammasome, thereby alleviating liver injury.
*Casp1↓,
*IL1β↓,
*IL18↓,
*NLRP3↓,
*MDA↓, inhibiting oxidative stress and regulating the level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH)
*SOD↑,
*NRF2↑, luteolin promoted the activation of the Nrf2/ antioxidant response element (ARE) pathway and NF-κB cell apoptosis pathway, thereby reversing the decrease in Nrf2 levels(lead induced liver injury)
*ER Stress↓, down regulate the formation of nitrotyrosine (NT) and endoplasmic reticulum (ER) stress induced by acetaminophen, and alleviate liver injury
*ALAT↓, ↓ALT, AST, MDA, iNOS, NLRP3 ↑GSH, SOD, Nrf2
*AST↓,
*iNOS↓,
*IL6↓, ↓TXNIP, NLRP3, TNF-α, IL-6 ↑HO-1, NQO1
*HO-1↑,
*NQO1↑,
*PPARα↑, ↓TNF-α, IL-6 IL-1β, Bax ↑PPARα
*ATF4↓, ↓ALT, AST, TNF-α, IL-6, MDA, ATF-4, CHOP ↑GSH, SOD
*CHOP/DDIT3↓,
*Inflam↓, Luteolin ameliorates MAFLD through anti-inflammatory and antioxidant effects
*antiOx↑,
*GutMicro↑, luteolin could significantly enrich more than 10% of intestinal bacterial species, thereby increasing the abundance of ZO-1, down regulating intestinal permeability and plasma lipopolysaccharide

2919-

LT,

Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence

Review,

Var,

RadioS↑, it can be used as an adjuvant to radio-chemotherapy and helps to ameliorate cancer complications
ChemoSen↑,
chemoP↑,
*lipid-P↓, ↓LPO, ↑CAT, ↑SOD, ↑GPx, ↑GST, ↑GSH, ↓TNF-α, ↓IL-1β, ↓Caspase-3, ↑IL-10
*Catalase↑,
*SOD↑,
*GPx↑,
*GSTs↑,
*GSH↑,
*TNF-α↓,
*IL1β↓,
*Casp3↓,
*IL10↑,
NRF2↓, Lung cancer model ↓Nrf2, ↓HO-1, ↓NQO1, ↓GSH
HO-1↓,
NQO1↓,
GSH↓,
MET↓, Lung cancer model ↓MET, ↓p-MET, ↓p-Akt, ↓HGF
p‑MET↓,
p‑Akt↓,
HGF/c-Met↓,
NF-kB↓, Lung cancer model ↓NF-κB, ↓Bcl-XL, ↓MnSOD, ↑Caspase-8, ↑Caspase-3, ↑PARP
Bcl-2↓,
SOD2↓,
Casp8↑,
Casp3↑,
PARP↑,
MAPK↓, LLC-induced BCP mouse model ↓p38 MAPK, ↓GFAP, ↓IBA1, ↓NLRP3, ↓ASC, ↓Caspase1, ↓IL-1β
NLRP3↓,
ASC↓,
Casp1↓,
IL6↓, Lung cancer model ↓TNF‑α, ↓IL‑6, ↓MuRF1, ↓Atrogin-1, ↓IKKβ, ↓p‑p65, ↓p-p38
IKKα↓,
p‑p65↓,
p‑p38↑,
MMP2↓, Lung cancer model ↓MMP-2, ↓ICAM-1, ↓EGFR, ↓p-PI3K, ↓p-Akt
ICAM-1↓,
EGFR↑,
p‑PI3K↓,
E-cadherin↓, Lung cancer model ↑E-cadherin, ↑ZO-1, ↓N-cadherin, ↓Claudin-1, ↓β-Catenin, ↓Snail, ↓Vimentin, ↓Integrin β1, ↓FAK
ZO-1↑,
N-cadherin↓,
CLDN1↓,
β-catenin/ZEB1↓,
Snail↓,
Vim↑,
ITGB1↓,
FAK↓,
p‑Src↓, Lung cancer model ↓p-FAK, ↓p-Src, ↓Rac1, ↓Cdc42, ↓RhoA
Rac1↓,
Cdc42↓,
Rho↓,
PCNA↓, Lung cancer model ↓Cyclin B1, ↑p21, ↑p-Cdc2, ↓Vimentin, ↓MMP9, ↑E-cadherin, ↓AIM2, ↓Pro-caspase-1, ↓Caspase-1 p10, ↓Pro-IL-1β, ↓IL-1β, ↓PCNA
Tyro3↓, Lung cancer model ↓TAM RTKs, ↓Tyro3, ↓Axl, ↓MerTK, ↑p21
AXL↓,
CEA↓, B(a)P induced lung carcinogenesis ↓CEA, ↓NSE, ↑SOD, ↑CAT, ↑GPx, ↑GR, ↑GST, ↑GSH, ↑Vitamin E, ↑Vitamin C, ↓PCNA, ↓CYP1A1, ↓NF-kB
NSE↓,
SOD↓,
Catalase↓,
GPx↓,
GSR↓,
GSTs↓,
GSH↓,
VitE↓,
VitC↓,
CYP1A1↓,
cFos↑, Lung cancer model ↓Claudin-2, ↑p-ERK1/2, ↑c-Fos
AR↓, ↓Androgen receptor
AIF↑, Lung cancer model ↑Apoptosis-inducing factor protein
p‑STAT6↓, ↓p-STAT6, ↓Arginase-1, ↓MRC1, ↓CCL2
p‑MDM2↓, Lung cancer model ↓p-PI3K, ↓p-Akt, ↓p-MDM2, ↑p-P53, ↓Bcl-2, ↑Bax
NOTCH1↓, Lung cancer model ↑Bax, ↑Cleaved-caspase 3, ↓Bcl2, ↑circ_0000190, ↓miR-130a-3p, ↓Notch-1, ↓Hes-1, ↓VEGF
VEGF↓,
H3↓, Lung cancer model ↑Caspase 3, ↑Caspase 7, ↓H3 and H4 HDAC activities
H4↓,
HDAC↓,
SIRT1↓, Lung cancer model ↑Bax/Bcl-2, ↓Sirt1
ROS↑, Lung cancer model ↓NF-kB, ↑JNK, ↑Caspase 3, ↑PARP, ↑ROS, ↓SOD
DR5↑, Lung cancer model ↑Caspase-8, ↑Caspase-3, ↑Caspase-9, ↑DR5, ↑p-Drp1, ↑Cytochrome c, ↑p-JNK
Cyt‑c↑,
p‑JNK↑,
PTEN↓, Lung cancer model 1/5/10/30/50/80/100 μmol/L ↑Cleaved caspase-3, ↑PARP, ↑Bax, ↓Bcl-2, ↓EGFR, ↓PI3K/Akt/PTEN/mTOR, ↓CD34, ↓PCNA
mTOR↓,
CD34↓,
FasL↑, Lung cancer model ↑DR 4, ↑FasL, ↑Fas receptor, ↑Bax, ↑Bad, ↓Bcl-2, ↑Cytochrome c, ↓XIAP, ↑p-eIF2α, ↑CHOP, ↑p-JNK, ↑LC3II
Fas↑,
XIAP↓,
p‑eIF2α↑,
CHOP/DDIT3↑,
LC3II↑,
PD-1↓, Lung cancer model ↓PD-L1, ↓STAT3, ↑IL-2
STAT3↓,
IL2↑,
EMT↓, Luteolin exerts anticancer activity by inhibiting EMT, and the possible mechanisms include the inhibition of the EGFR-PI3K-AKT and integrin β1-FAK/Src signaling pathways
cachexia↓, luteolin could be a potential safe and efficient alternative therapy for the treatment of cancer cachexi
BioAv↑, A low-energy blend of castor oil, kolliphor and polyethylene glycol 200 increases the solubility of luteolin by a factor of approximately 83
*Half-Life↝, ats administered an intraperitoneal injection of luteolin (60 mg/kg) absorbed it rapidly as well, with peak levels reached at 0.083 h (71.99 ± 11.04 μg/mL) and a prolonged half-life (3.2 ± 0.7 h)
*eff↑, Luteolin chitosan-encapsulated nano-emulsions increase trans-nasal mucosal permeation nearly 6-fold, drug half-life 10-fold, and biodistribution of luteolin in brain tissue 4.4-fold after nasal administration

3363-

QC,

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation

in-vitro,

Nor,

HBMECs

 (0.1, 0.5, 1 μmol/L)

*Apoptosis↓, Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis.
*angioG↑,
*NRF2↑, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression.
*Keap1↓,
*ATF6↓,
*GRP78/BiP↓,
*CLDN5↑, quercetin could increase the expression of Claudin-5 and Zonula occludens-1.
*ZO-1↑,
*MMP↑, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis.
*BBB↑, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.
*ROS↓, Quercetin Could Inhibit Oxidative Stress
*ER Stress↓, In our study, ER stress was activated by H/R, and the levels of ATF6 and GRP78 were increased. Quercetin at 1 μmol/L was able to significantly reduce the protein levels of both, inhibit ER stress, and protect HBMECs from H/R injury

1136-

SFN,

Sulforaphane inhibits epithelial-mesenchymal transition by activating extracellular signal-regulated kinase 5 in lung cancer cells

in-vitro,

Lung,

in-vivo,

NA,

Xenograft model

TumCMig↓,
E-cadherin↑,
ZO-1↑,
N-cadherin↓,
Snail↓, Snail1
ERK5↑,
EMT↓,

5934-

TV,

Protective Effects of Natural Antioxidants on Inflammatory Bowel Disease: Thymol and Its Pharmacological Properties

Review,

Var,

*Inflam↓, anti-inflammation, anti-oxidation, anti-bacteria, anti-fungal, and anti-tumor potential
*antiOx↑,
*Bacteria↓,
AntiTum↑,
*toxicity∅, A high dose of thymol up to 500 mg/kg diet has been shown to have no toxicity
*IBI↑, thymol improves intestinal integrity and alleviates intestinal injury via the regulation of the immune response and oxidation-reduction homeostasis
*ZO-1↑, increasing the expression of the tight junction protein zonula occludens-1 (ZO-1) and occludins
*OCLN↑,
*COX1↑, up-regulates cyclooxygenase-1 (COX1) activity
*TLR4↓, thymol inhibits TLR4 expression and then inhibits the activation of NF-κB signaling, which reduces the production of inflammatory cytokines, such as TNF-α and IL-1β [58,59]
*NF-kB↓,
*TNF-α↓,
*IL1β↓,
*TAC↑, Thymol Improves Anti-Oxidant Capacity in IBD
*NRF2↑, Studies have indicated that thymol activates Nrf2 signaling in different tissues
*GutMicro↑, Thymol Changes Gut Microbes and Prevents Pathogen Infection. thymol also promoted the colonization of beneficial bacteria, such as Clostridium, Lactobacillus, and Bacteroides, to improve gut health

1740-

VitD3,

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

Review,

Var,

Risk↓, An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%.
eff↑, In 1936, Peller reported that people who developed skin cancer from light exposure, such as from their occupation, had lower rates of internal cancers
eff↑, low rates(internal cancer) in three southwest states and high rates in approximately 15 northeast states
Risk↓, Inverse correlations were found for 11 cancers with respect to solar UVB doses for white Americans and several types of cancer for black Americans
Risk↓, It reported an 82% lower risk of breast cancer for 25(OH)D concentration >60 ng/mL versus <20 ng/mL
ChemoSen↑, Sensitization to Apoptosis, Combined Action with Chemotherapy and Radiotherapy
RadioS↑,
Cyt‑c↑, it favors the release of cytochrome C from mitochondria and the activation of caspases 3 and 9 that lead to apoptosis promoted by a variety of signals
Casp3↑,
Casp9↑,
hTERT/TERT↓, by downregulation of telomerase reverse transcriptase (hTERT) via the induction of miR-498
eff↑, In addition, 1,25-(OH)2D3 and metformin have additive/synergistic antiproliferative and proapoptotic effects in colon carcinoma and other types of cells, which are modulated but not hampered by TP53 status
E-cadherin↑, 1,25-(OH)2D3 upregulates an array of intercellular adhesion molecules that are constituents of adherens junctions and tight junctions, including E-cadherin, occludin, claudin-2 and -12, and ZO-1 and -2
CLDN2↑,
ZO-1↑,
Snail↓, 1,25-(OH)2D3 inhibits SNAIL1 and ZEB1 expression in non-small cell lung carcinoma cells
Zeb1↓,
Vim↓, vimentin downregulation
VEGF↓, 1,25-(OH)2D3 alone and more strongly in combination with cisplatin suppresses VEGF activity in ovarian cancer cells
NK cell↑, 1,25-(OH)2D3 is an enhancer of innate immune reactions against infections and tumor cells by activating the responsive cells (macrophages, natural killer (NK) cells, and neutrophils)
Risk↓, vitamin D deficiency promotes gut permeability, colon mucosa bacterial infiltration, and translocation of intestinal pathogens. These effects lead to changes in immune cell populations and gut inflammation, and cancer—an overall condition that is im
eff↑, Combination with immunotherapy

2368-

VitD3,

Vitamin D3 supplementation shapes the composition of gut microbiota and improves some obesity parameters induced by high-fat diet in mice

in-vivo,

Obesity,

Male C57BL/6 J mice

*Weight↓, VD3 supplementation reduced body weight and the levels of TG, TC, HDL-C, TNF-α, IL-1β and LPS, and increased ZO-1 in HFD-fed mice
*TNF-α↓,
*IL1β↓,
LPS↓,
*ZO-1↑,
*GutMicro↑, increased α-diversity, reduced F/B ratio and altered microbiota composition by increasing relative abundance of Bacteroidetes, Proteobacteria, Desulfovibrio, Dehalobacterium, Odoribacter, and Parabacteroides and reducing relative abundance of Firmic

1820-

VitK3,

Vitamin K3 (menadione) suppresses epithelial-mesenchymal-transition and Wnt signaling pathway in human colorectal cancer cells

in-vitro,

CRC,

SW480

in-vitro,

CRC,

SW-620

selectivity↑, Menadione showed cytotoxicity against human CRC cells (SW480 and SW620) and human primary colon cancer cells but was relatively ineffective against the cells from human normal colon (CRL-1790)
TumCI↓, Menadione suppressed invasion, migration and epithelial-mesenchymal transition in human CRC cells
TumCMig↓,
EMT↓,
E-cadherin↑, by upregulating the expression of E-cadherin (CDH1), ZO-1
ZO-1↑,
N-cadherin↓, and downregulating that of N-cadherin (CDH2), Vimentin (VIM), ZEB1, MMP2 and MMP9.
Vim↓,
Zeb1↓,
MMP2↓,
MMP9↓,
TOPflash↓, Menadione decreased TOPFlash/FOPFlash luciferase activity
β-catenin/ZEB1↓, β-catenin (CTNNB1), TCF7L2, Bcl9l, p300 (EP300) and cyclin D1 (CCND1) was suppressed
p300↓,
cycD1/CCND1↓,
TumCCA↑, SubG0 phase of cell cycle

Showing Research Papers: 1 to 21 of 21

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 21

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

IL1RL1/ST2↓, 1, ILC2↓, 1, Stroke↓, 1,

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1, antiOx↑, 4, Catalase↑, 3, GPx↑, 2, GSH↑, 4, GSTs↑, 1, HO-1↑, 2, Keap1↓, 1, lipid-P↓, 2, MDA↓, 3, NQO1↑, 1, NRF2↑, 5, ROS↓, 5, SOD↑, 4, TAC↑, 1,

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↑, 1,

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 2, AMPK↑, 1, PPARα↑, 1, SIRT1↑, 2, SREBP1/SREBF1↓, 1,

Cell Death(tgid=5) ⓘ

p‑Akt↑, 1, Apoptosis↓, 2, BAX↓, 1, Bcl-2↑, 1, Casp1↓, 2, Casp3↓, 2, iNOS↓, 2, iNOS↑, 1,

Kinase & Signal Transduction(tgid=6) ⓘ

HCAR2↑, 1,

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 1,

Protein Folding & ER Stress(tgid=8) ⓘ

ATF6↓, 1, CHOP/DDIT3↓, 1, ER Stress↓, 2, GRP78/BiP↓, 1,

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1, GSK‐3β↓, 1, GSK‐3β↑, 1, p‑GSK‐3β↑, 1,

Migration(tgid=13) ⓘ

5LO↓, 1, BACH1↓, 1, Ca+2↝, 1, cal2↓, 1, CLDN1↑, 2, E-cadherin↑, 2, F-actin↓, 1, MUC1↑, 1, N-cadherin↓, 1, Snail↓, 1, TumCMig↓, 1, TXNIP↓, 1, VCAM-1↓, 1, Vim↓, 1, ZO-1↑, 11,

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↑, 1, ATF4↓, 1, CLDN5↑, 1, NO↓, 1,

Barriers & Transport(tgid=15) ⓘ

BBB↑, 1, BBB↝, 2, CLDN3↑, 1, IBI↑, 2, OCLN↑, 3,

Immune & Inflammatory Signaling(tgid=16) ⓘ

ASC↓, 1, COX1↑, 1, COX2/PTGS2↓, 4, HCAR2↑, 1, ICAM-1↓, 1, IFN-γ↓, 2, IL10↑, 2, IL18↓, 1, IL1β↓, 7, IL2↓, 1, IL33↓, 1, IL6↓, 5, IL8↓, 1, Imm↑, 1, Imm⇅, 1, Inflam↓, 7, NF-kB↓, 6, PGE2↓, 1, TLR4↓, 4, TNF-α↓, 6,

Synaptic & Neurotransmission(tgid=18) ⓘ

BDNF↑, 1, NGF↑, 1, TrkB↑, 1,

Protein Aggregation(tgid=19) ⓘ

NLRP3↓, 2,

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1, BioAv↑, 1, eff↓, 1, eff↑, 2, Half-Life↝, 1,

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 2, AST↓, 3, GutMicro↑, 5, IL6↓, 5,

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1, AntiDiabetic↑, 1, cardioP↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 1, RenoP↓, 1, RenoP↑, 1, toxicity↓, 2, toxicity∅, 1, Weight↓, 1, Wound Healing↑, 1,

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1, Bacteria↓, 1,
Total Targets: 114

Scientific Paper Hit Count for: ZO-1, Zonula occludens-1

2 Luteolin
2 Vitamin D3
1 Aloe anthraquinones
1 Baicalin
1 Baicalein
1 Butyrate
1 Carvacrol
1 Chlorogenic acid
1 Curcumin
1 Fisetin
1 Fucoidan
1 Grapeseed extract
1 Hydrogen Gas
1 Hyperoside
1 isoorientin
1 Quercetin
1 Sulforaphane (mainly Broccoli)
1 Thymol-Thymus vulgaris
1 VitK3,menadione

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#:%  Target#:674  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

ZO-1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Protein Folding & ER Stress(tgid=8) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Synaptic & Neurotransmission(tgid=18) ⓘ

Protein Aggregation(tgid=19) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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