Luteolin / ROS 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↓">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


ROS, Reactive Oxygen Species: Click to Expand ⟱
Source: HalifaxProj (inhibit)
Type:
Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer.
ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations.
However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS.
-mitochondria is the main source of reactive oxygen species (ROS) (and the ETC is heavily related)

"Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways."
"During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity."
"ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−".
"Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules."

Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper." > Ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea.
Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells."

Majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers.
-It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis.

Note: Products that may raise ROS can be found using this database, by:
Filtering on the target of ROS, and selecting the Effect Direction of ↑

Targets to raise ROS (to kill cancer cells):
• NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS.
    -Targeting NOX enzymes can increase ROS levels and induce cancer cell death.
    -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS
• Mitochondrial complex I: Inhibiting can increase ROS production
• P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes)
• Nrf2 inhibition: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels
• Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels
• Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels
• SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels
• PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels
• HIF-1α inhibition: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS
• Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production.
-Inhibiting fatty acid oxidation can increase ROS levels
• ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels
• Autophagy: process by which cells recycle damaged organelles and proteins.
-Inhibiting autophagy can increase ROS levels and induce cancer cell death.
• KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes.
    -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death.
• DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels
• PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels
• SIRT1 inhibition:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels
• AMPK activation: regulates energy metabolism and can increase ROS levels when activated.
• mTOR inhibition: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels
• HSP90 inhibition: regulates protein folding and can increase ROS levels when inhibited.
• Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels
• Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS.
    -Increasing lipid peroxidation can increase ROS levels
• Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation.
    -Increasing ferroptosis can increase ROS levels
• Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability.
    -Opening the mPTP can increase ROS levels
• BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited.
• Caspase-independent cell death: a form of cell death that is regulated by ROS.
    -Increasing caspase-independent cell death can increase ROS levels
• DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS
• Epigenetic regulation: process by which gene expression is regulated.
    -Increasing epigenetic regulation can increase ROS levels

-PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS)

ProOxidant Strategy:(inhibit the Mevalonate Pathway (likely will also inhibit GPx)
-HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more
-Atorvastatin typically 40-80mg/day, -Dipyridamole typically 200mg 2x/day Combined effect research
-Lycopene typically 100mg/day range (note debatable as it mainly lowers NRF2)

Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy 
ROS-Inducing Interventions in Cancer — Canonical + Mechanistic Reference
-generated from AI and Cancer database
ROS rating:  +++ strong | ++ moderate | + weak | ± mixed | 0 none
NRF2:        ↓ suppressed | ↑ activated | ± mixed | 0 none
Conditions:  [D] dose  [Fe] metal  [M] metabolic  [O₂] oxygen
             [L] light [F] formulation [T] tumor-type [C] combination




Item ROS↑ NRF2 Condition Mechanism Class Remarks 



ROS">Piperlongumine
+++ ↓ [D][T] ROS-dominant






ROS">Shikonin
+++↓/±[D][T]ROS-dominant






ROS">Vitamin K3 (menadione)
+++↓[D]ROS-dominant






ROS">Copper (ionic / nano)
+++↓[Fe][F]ROS-dominant






ROS">Sodium Selenite
+++↓[D]ROS-dominant






ROS">Juglone
+++↓[D]ROS-dominant






ROS">Auranofin
+++↓[D]ROS-dominant






ROS">Photodynamic Therapy (PDT)
+++0[L][O₂]ROS-dominant






ROS">Radiotherapy / Radiation
+++0[O₂]ROS-dominant






ROS">Doxorubicin
+++↓[D]ROS-dominant






ROS">Cisplatin
++↓[D][T]ROS-dominant






ROS">Salinomycin
++↓[D][T]ROS-dominant






ROS">Artemisinin / DHA
++↓[Fe][T]ROS-dominant






ROS">Sulfasalazine
++↓[C][T]ROS-dominant






ROS">FMD / fasting
++↓[M][C][O₂]ROS-dominant






ROS">Vitamin C (pharmacologic)
++↓[Fe][D]ROS-dominant






ROS">Silver nanoparticles
++±[F][D]ROS-dominant






ROS">Gambogic acid
++↓[D][T]ROS-dominant






ROS">Parthenolide
++↓[D][T]ROS-dominant






ROS">Plumbagin
++↓[D]ROS-dominant






ROS">Allicin
++↓[D]ROS-dominant






ROS">Ashwagandha (Withaferin A)
++↓[D][T]ROS-dominant






ROS">Berberine
++↓[D][M]ROS-dominant






ROS">PEITC
++↓[D][C]ROS-dominant






ROS">Methionine restriction
+↓[M][C][T]ROS-secondary






ROS">DCA
+±[M][T]ROS-secondary






ROS">Capsaicin
+±[D][T]ROS-secondary






ROS">Galloflavin
+0[D]ROS-secondary






ROS">Piperine
+±[D][F]ROS-secondary






ROS">Propyl gallate
+↓[D]ROS-secondary






ROS">Scoulerine
+?[D][T]ROS-secondary






ROS">Thymoquinone
±±[D][T]Dual redox






ROS">Emodin
±±[D][T]Dual redox






ROS">Alpha-lipoic acid (ALA)
±↑[D][M]NRF2-dominant






ROS">Curcumin
±↑/↓[D][F]NRF2-dominant






ROS">EGCG
±↑/↓[D][O₂]NRF2-dominant






ROS">Quercetin
±↑/↓[D][Fe]NRF2-dominant






ROS">Resveratrol
±↑[D][M]NRF2-dominant






ROS">Sulforaphane
±↑↑[D]NRF2-dominant






ROS">Lycopene
0↑—Antioxidant






ROS">Rosmarinic acid
0↑—Antioxidant






ROS">Citrate
00—Neutral


Scientific Papers found: Click to Expand⟱
2625- Ba,  LT,    Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte
- in-vivo, Stroke, NA
*lipid-P↓, *ACSL4∅, *NRF2∅, *GPx4∅, *Ferroptosis↓, *ROS↓, *MDA↓, *eff↑, *HO-1∅,
2919- LT,    Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence
- Review, Var, NA
RadioS↑, ChemoSen↑, chemoP↑, *lipid-P↓, *Catalase↑, *SOD↑, *GPx↑, *GSTs↑, *GSH↑, *TNF-α↓, *IL1β↓, *Casp3↓, *IL10↑, NRF2↓, HO-1↓, NQO1↓, GSH↓, MET↓, p‑MET↓, p‑Akt↓, HGF/c-Met↓, NF-kB↓, Bcl-2↓, SOD2↓, Casp8↑, Casp3↑, PARP↑, MAPK↓, NLRP3↓, ASC↓, Casp1↓, IL6↓, IKKα↓, p‑p65↓, p‑p38↑, MMP2↓, ICAM-1↓, EGFR↑, p‑PI3K↓, E-cadherin↓, ZO-1↑, N-cadherin↓, CLDN1↓, β-catenin/ZEB1↓, Snail↓, Vim↑, ITGB1↓, FAK↓, p‑Src↓, Rac1↓, Cdc42↓, Rho↓, PCNA↓, Tyro3↓, AXL↓, CEA↓, NSE↓, SOD↓, Catalase↓, GPx↓, GSR↓, GSTs↓, GSH↓, VitE↓, VitC↓, CYP1A1↓, cFos↑, AR↓, AIF↑, p‑STAT6↓, p‑MDM2↓, NOTCH1↓, VEGF↓, H3↓, H4↓, HDAC↓, SIRT1↓, ROS↑, DR5↑, Cyt‑c↑, p‑JNK↑, PTEN↓, mTOR↓, CD34↓, FasL↑, Fas↑, XIAP↓, p‑eIF2α↑, CHOP↑, LC3II↑, PD-1↓, STAT3↓, IL2↑, EMT↓, cachexia↓, BioAv↑, *Half-Life↝, *eff↑,
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↑,
2921- LT,    Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies
- Review, Nor, NA
*hepatoP↑, *AMPK↑, *SIRT1↑, *ROS↓, STAT3↓, TNF-α↓, NF-kB↓, *IL2↓, *IFN-γ↓, *GSH↑, *SREBP1↓, *ZO-1↑, *TLR4↓, BAX↑, Bcl-2↓, XIAP↓, Fas↑, Casp8↑, Beclin-1↑, *TXNIP↓, *Casp1↓, *IL1β↓, *IL18↓, *NLRP3↓, *MDA↓, *SOD↑, *NRF2↑, *ER Stress↓, *ALAT↓, *AST↓, *iNOS↓, *IL6↓, *HO-1↑, *NQO1↑, *PPARα↑, *ATF4↓, *CHOP↓, *Inflam↓, *antiOx↑, *GutMicro↑,
2918- LT,    Luteolin inhibits melanoma growth in vitro and in vivo via regulating ECM and oncogenic pathways but not ROS
- in-vitro, Melanoma, A375 - in-vivo, Melanoma, NA - in-vitro, Melanoma, SK-MEL-28
TumCG↓, ROS↑, ECM/TCF↓,
2917- LT,  Rad,    Luteolin acts as a radiosensitizer in non‑small cell lung cancer cells by enhancing apoptotic cell death through activation of a p38/ROS/caspase cascade
- in-vitro, Lung, NA
Bcl-2↓, Casp3↑, Casp8↑, Casp9↑, p‑p38↑, ROS↑, RadioS↑,
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↑,
2915- LT,    Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells
- in-vitro, Colon, HT29 - in-vitro, CRC, SNU-407 - in-vitro, Nor, FHC
DNMTs↓, TET1↑, NRF2↑, HDAC↓, tumCV↓, BAX↑, Casp9↑, Casp3↑, Bcl-2↓, ROS↓, GSS↑, Catalase↑, HO-1↑, DNMT1↓, DNMT3A↓, TET1↑, TET3↑, TET2↓, P53↑, P21↑,
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↓,
2913- LT,    Luteolin induces apoptosis by impairing mitochondrial function and targeting the intrinsic apoptosis pathway in gastric cancer cells
- in-vitro, GC, HGC27 - in-vitro, BC, MCF-7 - in-vitro, GC, MKN45
TumCP↓, MMP↓, Apoptosis↑, ROS↑, SOD↓, ATP↓, Bax:Bcl2↑, TumCCA↑,
2912- LT,    Luteolin: a flavonoid with a multifaceted anticancer potential
- Review, Var, NA
ROS↑, TumCCA↑, TumCP↓, angioG↓, ER Stress↑, mtDam↑, PERK↑, ATF4↑, eIF2α↑, cl‑Casp12↑, EMT↓, E-cadherin↑, N-cadherin↓, Vim↓, *neuroP↑, NF-kB↓, PI3K↓, Akt↑, XIAP↓, MMP↓, Ca+2↑, BAX↑, Casp3↑, Casp9↑, Bcl-2↓, Cyt‑c↑, IronCh↑, SOD↓, *ROS↓, *LDHA↑, *SOD↑, *GSH↑, *BioAv↓, Telomerase↓, cMyc↓, hTERT/TERT↓, DR5↑, Fas↑, FADD↑, BAD↑, BOK↑, BID↑, NAIP↓, Mcl-1↓, CDK2↓, CDK4↓, MAPK↓, AKT1↓, Akt2↓, *Beclin-1↓, Hif1a↓, LC3II↑, Beclin-1↑,
2930- LT,    Luteolin confers renoprotection against ischemia–reperfusion injury via involving Nrf2 pathway and regulating miR320
- in-vitro, Nor, NA
*RenoP↑, *ROS↓, *antiOx↑, *NRF2↓,
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↑,
4338- LT,    Luteolin: a natural product with multiple mechanisms for atherosclerosis
- Review, NA, NA
*Inflam↓, *ROS↓, *PDGF↓, *lipid-P↓, *AMPK↑, *SIRT1↑, *AntiAg↑,
4339- LT,    Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis
- in-vivo, NA, NA
*AntiAg↑, *ROS↓,
1084- LT,  CHr,    Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells
- in-vitro, Nor, RAW264.7
*COX2↓, *COX2∅, *PGE2↓, *ROS↓,
1100- LT,    Luteolin, a flavonoid, as an anticancer agent: A review
- Review, NA, NA
TumCP↓, TumCCA↑, Apoptosis↑, EMT↓, E-cadherin↑, N-cadherin↓, Snail↓, Vim↓, ROS↑, ER Stress↑, mtDam↑, p‑eIF2α↝, p‑PERK↝, p‑CHOP↝, p‑ATF4↝, cl‑Casp12↝,
2911- LT,    Luteolin targets MKK4 to attenuate particulate matter-induced MMP-1 and inflammation in human keratinocytes
- in-vitro, Nor, HaCaT
*MMP1↓, *COX2↓, *IL6↓, *AP-1↓, *NF-kB↓, *ROS↓, *p‑MKK4↑, *p‑JNK↓, *p‑p38↓,
2903- LT,    Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vivo, NA, NA
ER Stress↑, ROS↑, PERK↑, eIF2α↑, ATF4↑, CHOP↑, Casp12↑, eff↓, UPR↑, MMP↓, Cyt‑c↑, Bcl-2↓, BAX↑, TumCG↓, Weight∅, ALAT∅, AST∅,
2904- LT,    Luteolin from Purple Perilla mitigates ROS insult particularly in primary neurons
- in-vitro, Park, SK-N-SH - in-vitro, AD, NA
*ROS↓, *neuroP↑, *MMP↑, *Catalase↑, *GSH↑, selectivity↑, *eff↑, *Cyt‑c↓,
2905- LT,    Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions
- in-vivo, NA, HMrSV5
*ROS↓, *p‑Akt↓, *Vim↓, *E-cadherin↑, *PI3K↓,
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↑,
2907- LT,    Protective effect of luteolin against oxidative stress‑mediated cell injury via enhancing antioxidant systems
- in-vitro, Nor, NA
*ROS↓, *Casp9↓, *Casp3↓, *Bcl-2↑, *BAX↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, *HO-1↑, *antiOx↑, *lipid-P↓, *p‑γH2AX↓, eff↑,
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 24 of 24

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 24

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx⇅, 1,   Catalase↓, 2,   Catalase↑, 1,   CYP1A1↓, 2,   GPx↓, 1,   GSH↓, 2,   GSR↓, 1,   GSS↑, 1,   GSTs↓, 2,   HO-1↓, 2,   HO-1↑, 1,   NQO1↓, 1,   NRF2↓, 3,   NRF2↑, 2,   ROS↓, 2,   ROS↑, 11,   SOD↓, 4,   SOD2↓, 1,   Trx1↑, 1,   TrxR1↓, 1,   VitC↓, 1,   VitE↓, 1,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 1,   BOK↑, 1,   CDC2↓, 2,   MMP↓, 4,   mtDam↑, 2,   XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

AKT1↓, 2,   ALAT∅, 1,   cMyc↓, 2,   p‑cMyc↑, 1,   FASN↓, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Akt↑, 1,   p‑Akt↓, 2,   APAF1↑, 1,   Apoptosis↑, 4,   ATF2↓, 1,   BAD↑, 1,   BAX↑, 7,   Bax:Bcl2↑, 1,   Bcl-2↓, 7,   Bcl-xL↓, 1,   BID↑, 1,   Casp↑, 1,   Casp1↓, 1,   Casp12↑, 1,   cl‑Casp12↑, 1,   cl‑Casp12↝, 1,   Casp3↑, 5,   cl‑Casp3↑, 1,   Casp8↑, 3,   cl‑Casp8↑, 1,   Casp9↑, 4,   cl‑Casp9↑, 1,   proCasp9↓, 1,   Cyt‑c↑, 4,   DR5↑, 5,   FADD↑, 1,   Fas↑, 4,   FasL↑, 1,   HGF/c-Met↓, 1,   hTERT/TERT↓, 3,   iNOS↓, 1,   JNK↑, 2,   p‑JNK↑, 1,   MAPK↓, 3,   MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 2,   p‑MDM2↓, 1,   NAIP↓, 1,   NICD↓, 1,   p27↑, 1,   p‑p38↑, 2,   survivin↓, 1,   Telomerase↓, 2,   YAP/TEAD↓, 1,  

Transcription & Epigenetics ⓘ

H3↓, 1,   H4↓, 1,   TET3↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 2,   p‑CHOP↝, 1,   eIF2α↑, 2,   p‑eIF2α↑, 1,   p‑eIF2α↝, 1,   ER Stress↑, 4,   PERK↑, 2,   p‑PERK↝, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 3,   BNIP3↑, 1,   LC3B-II↑, 1,   LC3II↑, 2,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 1,   P53↑, 4,   PARP↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 5,   CDK4↓, 1,   cycA1/CCNA1↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 1,   P21↑, 3,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   cFos↑, 1,   EMT↓, 5,   ERK↓, 2,   p‑ERK↓, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 2,   IGF-1↓, 1,   mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↓, 2,   PI3K↓, 4,   p‑PI3K↓, 1,   PTEN↓, 1,   RAS↓, 1,   p‑Src↓, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   p‑STAT6↓, 1,   TAZ↓, 1,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 2,   Wnt↓, 1,  

Migration ⓘ

AEG1↓, 1,   Akt2↓, 1,   AXL↓, 1,   Ca+2↑, 2,   Cdc42↓, 1,   CEA↓, 1,   CLDN1↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 4,   FAK↓, 3,   ITGB1↓, 1,   MET↓, 1,   p‑MET↓, 1,   MMP1↓, 1,   MMP2↓, 3,   MMP9↓, 3,   N-cadherin↓, 5,   PDGF↓, 1,   PKCδ↓, 1,   Rac1↓, 1,   Rho↓, 1,   Snail↓, 3,   TET1↑, 2,   TIMP1↑, 1,   TIMP2↑, 1,   TumCP↓, 5,   TumMeta↓, 1,   Twist↓, 2,   Tyro3↓, 1,   Vim↓, 3,   Vim↑, 1,   ZO-1↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   ATF4↑, 2,   p‑ATF4↝, 1,   ECM/TCF↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   Hif1a↓, 2,   VEGF↓, 4,   VEGFR2↓, 2,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   COX2↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL1↓, 1,   IL2↑, 1,   IL6↓, 2,   NF-kB↓, 8,   p‑NF-kB↑, 1,   p‑p65↓, 1,   PD-1↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 3,   CYP1A2↓, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 1,   Half-Life↝, 1,   MDR1↓, 1,   P450↓, 1,   RadioS↑, 3,   selectivity↑, 1,   TET2↓, 1,  

Clinical Biomarkers ⓘ

ALAT∅, 1,   AR↓, 2,   AST∅, 1,   CEA↓, 1,   EGFR↓, 1,   EGFR↑, 1,   p‑EGFR↓, 1,   GutMicro↑, 1,   hTERT/TERT↓, 3,   IL6↓, 2,   NSE↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cachexia↓, 1,   cardioP↑, 1,   chemoP↑, 2,   Weight∅, 1,  
Total Targets: 228

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 6,   Catalase↑, 5,   Ferroptosis↓, 1,   GPx↑, 2,   GPx4∅, 1,   GSH↑, 5,   GSR↑, 2,   GSTA1↑, 1,   GSTs↑, 2,   HO-1↑, 3,   HO-1∅, 1,   lipid-P↓, 5,   MDA↓, 2,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 3,   NRF2∅, 1,   ROS↓, 15,   SOD↑, 7,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   p‑MEK↓, 1,   p‑MKK4↑, 1,   MMP↑, 2,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4∅, 1,   ALAT↓, 1,   AMPK↑, 2,   CREB↑, 1,   LDHA↑, 1,   PPARα↑, 1,   PPARγ↑, 1,   SIRT1↑, 2,   SREBP1↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   BAX↓, 1,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Casp1↓, 1,   Casp3↓, 3,   Casp9↓, 1,   Casp9↑, 1,   Cyt‑c↓, 1,   Ferroptosis↓, 1,   iNOS↓, 1,   p‑JNK↓, 1,   p‑p38↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   ER Stress↓, 1,   GRP78/BiP↑, 1,   UPR↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,  

DNA Damage & Repair ⓘ

p‑γH2AX↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 1,   GSK‐3β↓, 1,   PI3K↓, 1,  

Migration ⓘ

AntiAg↑, 2,   AP-1↓, 1,   E-cadherin↑, 1,   MMP1↓, 1,   PDGF↓, 1,   TXNIP↓, 1,   Vim↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↓, 1,   NO↓, 1,  

Barriers & Transport ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   COX2∅, 1,   IFN-γ↓, 1,   IL10↑, 1,   IL18↓, 1,   IL1β↓, 3,   IL2↓, 1,   IL33↓, 1,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 4,   NF-kB↓, 2,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BDNF↑, 1,   tau↓, 1,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,   BACE↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 1,   BioAv↝, 1,   eff↑, 4,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BloodF↑, 1,   GutMicro↑, 1,   IL6↓, 3,  

Functional Outcomes ⓘ

cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 4,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 106

Scientific Paper Hit Count for: ROS, Reactive Oxygen Species
24 Luteolin
1 Baicalein
1 Radiotherapy/Radiation
1 Chrysin
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#:275  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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