Luteolin / ERK 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


ERK, ERK signaling: Click to Expand ⟱
Source:
Type:
MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.
Scientific Papers found: Click to Expand⟱
1539- Api,  LT,    Dietary flavones counteract phorbol 12-myristate 13-acetate-induced SREBP-2 processing in hepatic cells
- in-vitro, Liver, HepG2
SREBP2↓, eff↑, p‑MEK↓, p‑ERK↓,
2923- LT,    Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells
- in-vitro, NA, NA
Apoptosis↑, TumCD↑, Casp12↑, Casp9↑, Casp3↑, ER Stress↑, CHOP↑, GRP78/BiP↑, GRP94↑, cl‑ATF6↑, p‑eIF2α↑, MMP↓, JNK↓, p38↑, ERK↑, Cyt‑c↑,
2916- LT,    Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies
- Review, Var, NA - Review, AD, NA - Review, Park, NA
proCasp9↓, CDC2↓, CycB/CCNB1↓, Casp9↑, Casp3↑, Cyt‑c↑, cycA1/CCNA1↑, CDK2↓, APAF1↑, TumCCA↑, P53↑, BAX↑, VEGF↓, Bcl-2↓, Apoptosis↑, p‑Akt↓, p‑EGFR↓, p‑ERK↓, p‑STAT3↓, cardioP↑, Catalase↓, SOD↓, *BioAv↓, *antiOx↑, *ROS↓, *NO↓, *GSTs↑, *GSR↑, *SOD↑, *Catalase↑, *lipid-P↓, PI3K↓, Akt↓, CDK2↓, BNIP3↑, hTERT/TERT↓, DR5↑, Beclin-1↑, TNF-α↓, NF-kB↓, IL1↓, IL6↓, EMT↓, FAK↓, E-cadherin↑, MDM2↓, NOTCH↓, MAPK↑, Vim↓, N-cadherin↓, Snail↓, MMP2↓, Twist↓, MMP9↓, ROS↑, MMP↓, *AChE↓, *MMP↑, *Aβ↓, *neuroP↑, Trx1↑, ROS↓, *NRF2↑, NRF2↓, *BBB↑, ChemoSen↑, GutMicro↑,
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↓,
2906- LT,    Luteolin, a flavonoid with potentials for cancer prevention and therapy
- Review, Var, NA
*Inflam↓, AntiCan↑, antiOx⇅, Apoptosis↑, TumCP↓, TumMeta↓, angioG↓, PI3K↓, Akt↓, NF-kB↓, XIAP↓, P53↑, *ROS↓, *GSTA1↑, *GSR↑, *SOD↑, *Catalase↑, *other↓, ROS↑, Dose↝, chemoP↑, NF-kB↓, JNK↑, p27↑, P21↑, DR5↑, Casp↑, Fas↑, BAX↑, MAPK↓, CDK2↓, IGF-1↓, PDGF↓, EGFR↓, PKCδ↓, TOP1↓, TOP2↓, Bcl-xL↓, FASN↓, VEGF↓, VEGFR2↓, MMP9↓, Hif1a↓, FAK↓, MMP1↓, Twist↓, ERK↓, P450↓, CYP1A1↓, CYP1A2↓, TumCCA↑,
2908- LT,    Luteolin attenuates neutrophilic oxidative stress and inflammatory arthritis by inhibiting Raf1 activity
- in-vitro, Arthritis, NA
*ROS↓, *p‑ERK↓, *p‑MEK↓, *Raf↓,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx⇅, 1,   Catalase↓, 1,   CYP1A1↓, 1,   HO-1↓, 1,   NRF2↓, 2,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 3,   SOD↓, 1,   Trx1↑, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 2,   p‑MEK↓, 1,   MMP↓, 2,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

p‑cMyc↑, 1,   FASN↓, 1,   SREBP2↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   APAF1↑, 1,   Apoptosis↑, 3,   BAX↑, 3,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   cl‑Casp8↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   proCasp9↓, 1,   Cyt‑c↑, 2,   DR5↑, 3,   Fas↑, 1,   hTERT/TERT↓, 2,   iNOS↓, 1,   JNK↓, 1,   JNK↑, 2,   MAPK↓, 1,   MAPK↑, 1,   MDM2↓, 2,   NICD↓, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,   TumCD↑, 1,   YAP/TEAD↓, 1,  

Protein Folding & ER Stress ⓘ

cl‑ATF6↑, 1,   CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 1,   GRP94↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   BNIP3↑, 1,   LC3B-II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 3,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 4,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 1,   P21↑, 2,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   ERK↓, 2,   ERK↑, 1,   p‑ERK↓, 2,   p‑GSK‐3β↓, 1,   IGF-1↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 3,   RAS↓, 1,   p‑STAT3↓, 1,   TAZ↓, 1,   TOP1↓, 1,   TOP2↓, 1,   Wnt↓, 1,  

Migration ⓘ

AEG1↓, 1,   Ca+2↑, 1,   E-cadherin↑, 2,   FAK↓, 2,   MMP1↓, 1,   MMP2↓, 2,   MMP9↓, 3,   N-cadherin↓, 2,   PDGF↓, 1,   PKCδ↓, 1,   Snail↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 2,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 1,   p‑EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 3,   VEGFR2↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   IL1↓, 1,   IL6↓, 1,   NF-kB↓, 4,   p‑NF-kB↑, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↓, 1,   ChemoSen↑, 2,   CYP1A2↓, 1,   Dose↝, 1,   eff↑, 1,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   p‑EGFR↓, 1,   GutMicro↑, 1,   hTERT/TERT↓, 2,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoP↑, 1,  
Total Targets: 132

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 2,   GSR↑, 2,   GSTA1↑, 1,   GSTs↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 3,   SOD↑, 2,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

p‑MEK↓, 1,   MMP↑, 1,   Raf↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,  

Functional Outcomes ⓘ

neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 24

Scientific Paper Hit Count for: ERK, ERK signaling
6 Luteolin
1 Apigenin (mainly Parsley)
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#:105  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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