Luteolin / GSK‐3β Cancer Research Results

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


GSK‐3β, Glycogen synthase kinase (GSK)3β: Click to Expand ⟱
Source:
Type:
GSK3β is a crucial member of the Wnt/β-catenin-, hedgehog (Hh)-, notch- and c-myc-mediated major pro-oncogenic pathways, while also being a negative regulator of epithelial–mesenchymal transition (EMT). Accumulating evidence defines GSK3β as a potential therapeutic target in cancer, thus encouraging the development of GSK3β inhibitors for cancer treatment.
Glycogen synthase kinase 3 beta (GSK-3β) is a serine/threonine kinase that plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis. Its expression and activity have been implicated in several types of cancer, often with varying prognostic implications.

In many cancers, decreased GSK-3β activity is associated with poor prognosis, while in others, increased activity may correlate with aggressive disease.


Scientific Papers found: Click to Expand⟱
2922- LT,    Combination of transcriptomic and proteomic approaches helps unravel the mechanisms of luteolin in inducing liver cancer cell death via targeting AKT1 and SRC
- in-vitro, Liver, HUH7
Half-Life↝, TumCCA↑, AKT1↓, ATF2↓, NF-kB↓, GSK‐3β↓, cMyc↓, GSTs↓, TrxR1↓, ROS↑,
2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
*antiOx↑, *IronCh↑, *toxicity↓, *BioAv↓, *BioAv↑, DNAdam↑, TumCP↓, DR5↑, P53↑, JNK↑, BAX↑, cl‑Casp3↑, cl‑Casp8↑, cl‑Casp9↑, cl‑PARP↑, survivin↓, cycD1/CCND1↓, CycB/CCNB1↓, CDC2↓, P21↑, angioG↓, MMP2↓, AEG1↓, VEGF↓, VEGFR2↓, MMP9↓, CXCR4↓, PI3K↓, Akt↓, ERK↓, TumAuto↑, LC3B-II↑, EMT↓, E-cadherin↑, N-cadherin↓, Wnt↓, ROS↑, NICD↓, p‑GSK‐3β↓, iNOS↓, COX2↓, NRF2↑, Ca+2↑, ChemoSen↑, ChemoSen↓, IFN-γ↓, RadioS↑, MDM2↓, NOTCH1↓, AR↓, TIMP1↑, TIMP2↑, ER Stress↑, CDK2↓, Telomerase↓, p‑NF-kB↑, p‑cMyc↑, hTERT/TERT↓, RAS↓, YAP/TEAD↓, TAZ↓, NF-kB↓, NRF2↓, HO-1↓, MDR1↓,
4292- LT,    Luteolin for neurodegenerative diseases: a review
- Review, AD, NA - Review, Park, NA - Review, MS, NA - Review, Stroke, NA
*Inflam↓, *antiOx↑, *neuroP↑, *BioAv↝, *BBB↑, *TNF-α↓, *IL1β↓, *IL6↓, *IL8↓, *IL33↓, *NF-kB↓, *BACE↓, *ROS↓, *SOD↑, *HO-1↑, *NRF2↑, *Casp3↓, *Casp9↑, *Bax:Bcl2↓, *UPR↑, *GRP78/BiP↑, *Aβ↓, *GSK‐3β↓, *tau↓, *CREB↑, *ATP↑, *cognitive↑, *BloodF↑, *BDNF↑, *TrkB↑, *memory↑, *PPARγ↑, *eff↑,
4295- LT,    Luteolin Reduces Alzheimer’s Disease Pathologies Induced by Traumatic Brain Injury
- in-vivo, AD, NA
*Aβ↓, *GSK‐3β↓, *p‑tau↓, *BBB↑,

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 ⓘ

GSTs↓, 1,   HO-1↓, 1,   NRF2↓, 1,   NRF2↑, 1,   ROS↑, 2,   TrxR1↓, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 1,   cMyc↓, 1,   p‑cMyc↑, 1,  

Cell Death ⓘ

Akt↓, 1,   ATF2↓, 1,   BAX↑, 1,   cl‑Casp3↑, 1,   cl‑Casp8↑, 1,   cl‑Casp9↑, 1,   DR5↑, 1,   hTERT/TERT↓, 1,   iNOS↓, 1,   JNK↑, 1,   MDM2↓, 1,   NICD↓, 1,   survivin↓, 1,   Telomerase↓, 1,   YAP/TEAD↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

LC3B-II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   ERK↓, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   NOTCH1↓, 1,   PI3K↓, 1,   RAS↓, 1,   TAZ↓, 1,   Wnt↓, 1,  

Migration ⓘ

AEG1↓, 1,   Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   NF-kB↓, 2,   p‑NF-kB↑, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↓, 1,   ChemoSen↑, 1,   Half-Life↝, 1,   MDR1↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   hTERT/TERT↓, 1,  
Total Targets: 70

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,  

Core Metabolism/Glycolysis ⓘ

CREB↑, 1,   PPARγ↑, 1,  

Cell Death ⓘ

Bax:Bcl2↓, 1,   Casp3↓, 1,   Casp9↑, 1,  

Protein Folding & ER Stress ⓘ

GRP78/BiP↑, 1,   UPR↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 2,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL33↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,   tau↓, 1,   p‑tau↓, 1,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

BloodF↑, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   memory↑, 1,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 39

Scientific Paper Hit Count for: GSK‐3β, Glycogen synthase kinase (GSK)3β
4 Luteolin
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#:385  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

Home Page