Database Query Results : Luteolin, , β-catenin/ZEB1

LT, Luteolin: Click to Expand ⟱
Features:
Luteolin a Flavonoid found in celery, parsley, broccoli, onion leaves, carrots, peppers, cabbages, apple skins, and chrysanthemum flowers.
-MDR1 expression, MMP-9, IGF-1 and Epithelial to mesenchymal transition.

-Note half-life 2–3 hours
BioAv low, but could be improved with Res, or blend of castor oil, kolliphor and polyethylene glycol
Pathways:
- induce ROS production in cancer cell but a few reports of reduction. Always seems to reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMT1↓, DNMT3A↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, LDHA↓, HK2↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Luteolin — Cancer vs Normal Cell Effects
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR signaling ↔ adaptive suppression Driver Loss of survival and growth signaling Luteolin consistently suppresses PI3K/AKT signaling, explaining growth inhibition and apoptosis sensitization
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of inflammatory survival transcription NF-κB inhibition is a core, repeatedly observed luteolin effect
3 Reactive oxygen species (ROS) ↑ ROS (context- & dose-dependent) ↓ ROS / buffered Conditional Driver Biphasic redox modulation Luteolin can act as a pro-oxidant in cancer cells while remaining antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Secondary Execution of intrinsic apoptosis Mitochondrial apoptosis follows signaling and redox stress
5 STAT3 signaling ↓ STAT3 activation ↔ minimal Secondary Loss of proliferative and stemness signaling STAT3 suppression contributes to reduced invasion and CSC traits
6 Cell cycle regulation ↑ G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream pathway inhibition
7 Migration / invasion (EMT, MMP axis) ↓ migration & invasion ↔ Phenotypic Anti-metastatic phenotype Reduced EMT and protease activity limit invasiveness


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
2919- LT,    Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence
- Review, Var, NA
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↑,
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

1171- LT,    The inhibition of β-catenin activity by luteolin isolated from Paulownia flowers leads to growth arrest and apoptosis in cholangiocarcinoma
- in-vitro, CCA, NA
Wnt↓,
TumCCA↑, G2/M phase
Apoptosis↑,
TumCMig↓,
β-catenin/ZEB1↓, inhibitor of β-catenin
cMyc↓,
cycD1/CCND1↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   CYP1A1↓, 1,   GPx↓, 1,   GSH↓, 2,   GSR↓, 1,   GSTs↓, 1,   HO-1↓, 1,   NQO1↓, 1,   NRF2↓, 1,   ROS↑, 1,   SOD↓, 1,   SOD2↓, 1,   VitC↓, 1,   VitE↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   SIRT1↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   Apoptosis↑, 1,   Bcl-2↓, 1,   Casp1↓, 1,   Casp3↑, 1,   Casp8↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   FasL↑, 1,   HGF/c-Met↓, 1,   p‑JNK↑, 1,   MAPK↓, 1,   p‑MDM2↓, 1,   p‑p38↑, 1,  

Transcription & Epigenetics ⓘ

H3↓, 1,   H4↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   p‑eIF2α↑, 1,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,  

DNA Damage & Repair ⓘ

PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   cFos↑, 1,   EMT↓, 1,   HDAC↓, 1,   mTOR↓, 1,   NOTCH1↓, 1,   p‑PI3K↓, 1,   PTEN↓, 1,   p‑Src↓, 1,   STAT3↓, 1,   p‑STAT6↓, 1,   Wnt↓, 1,  

Migration ⓘ

AXL↓, 1,   Cdc42↓, 1,   CEA↓, 1,   CLDN1↓, 1,   E-cadherin↓, 1,   FAK↓, 1,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP2↓, 1,   N-cadherin↓, 1,   Rac1↓, 1,   Rho↓, 1,   Snail↓, 1,   TumCMig↓, 1,   Tyro3↓, 1,   Vim↑, 1,   ZO-1↑, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

EGFR↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   ICAM-1↓, 1,   IKKα↓, 1,   IL2↑, 1,   IL6↓, 1,   NF-kB↓, 1,   p‑p65↓, 1,   PD-1↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   CEA↓, 1,   EGFR↑, 1,   IL6↓, 1,   NSE↓, 1,  

Functional Outcomes ⓘ

cachexia↓, 1,   chemoP↑, 1,  
Total Targets: 95

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   lipid-P↓, 1,   SOD↑, 1,  

Cell Death ⓘ

Casp3↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL10↑, 1,   IL1β↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,   Half-Life↝, 1,  
Total Targets: 12

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
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#:118  Target#:342  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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