Luteolin / HO-1 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


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
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↑,
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↑,
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↓,
2927- LT,    Luteolin Causes 5′CpG Demethylation of the Promoters of TSGs and Modulates the Aberrant Histone Modifications, Restoring the Expression of TSGs in Human Cancer Cells
- in-vitro, Cerv, HeLa
TumCMig↓, DNMTs↓, HDAC↓, HATs↓, ac‑H3↓, ac‑H4↓, MMP2↓, MMP9↓, HO-1↓, E-cadherin↑, EZH2↓, HER2/EBBR2↓, IL18↓, IL8↓, IL2↓,
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↑,
2587- LT,    Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs
- in-vitro, Lung, A549
NRF2↓, GSH↓, ChemoSen↑, HO-1↓,
2588- LT,  Chemo,    Luteolin sensitizes two oxaliplatin-resistant colorectal cancer cell lines to chemotherapeutic drugs via inhibition of the Nrf2 pathway
- in-vitro, CRC, HCT116
NRF2↓, NQO1↓, HO-1↓, GSH↓, ChemoSen↑,
2589- LT,  Chemo,    Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway
- in-vitro, BC, MDA-MB-231
NRF2↓, HO-1↓, ChemoSen↑, CSCs↓, SIRT1↓,
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↑,

Showing Research Papers: 1 to 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↓, 1,   Catalase↑, 1,   CYP1A1↓, 1,   GPx↓, 1,   GSH↓, 4,   GSR↓, 1,   GSS↑, 1,   GSTs↓, 1,   HO-1↓, 6,   HO-1↑, 1,   NQO1↓, 2,   NRF2↓, 5,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 2,   SOD↓, 1,   SOD2↓, 1,   VitC↓, 1,   VitE↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC2↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

p‑cMyc↑, 1,   SIRT1↓, 2,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   BAX↑, 3,   Bcl-2↓, 3,   Casp1↓, 1,   Casp3↑, 2,   cl‑Casp3↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   DR5↑, 2,   Fas↑, 2,   FasL↑, 1,   HGF/c-Met↓, 1,   hTERT/TERT↓, 1,   iNOS↓, 1,   JNK↑, 1,   p‑JNK↑, 1,   MAPK↓, 1,   MDM2↓, 1,   p‑MDM2↓, 1,   NICD↓, 1,   p‑p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   H3↓, 1,   ac‑H3↓, 1,   H4↓, 1,   ac‑H4↓, 1,   HATs↓, 1,   TET3↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 2,   P53↑, 2,   PARP↑, 1,   cl‑PARP↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   P21↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   cFos↑, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 3,   mTOR↓, 1,   NOTCH1↓, 2,   PI3K↓, 1,   p‑PI3K↓, 1,   PTEN↓, 1,   RAS↓, 1,   p‑Src↓, 1,   STAT3↓, 2,   p‑STAT6↓, 1,   TAZ↓, 1,   Wnt↓, 1,  

Migration ⓘ

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

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↑, 1,   VEGF↓, 2,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC↓, 1,   COX2↓, 1,   CXCR4↓, 1,   ICAM-1↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL18↓, 1,   IL2↓, 1,   IL2↑, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 3,   p‑NF-kB↑, 1,   p‑p65↓, 1,   PD-1↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 5,   eff↑, 1,   MDR1↓, 1,   RadioS↑, 2,   TET2↓, 1,  

Clinical Biomarkers ⓘ

AR↓, 2,   CEA↓, 1,   EGFR↑, 1,   EZH2↓, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 1,   NSE↓, 1,  

Functional Outcomes ⓘ

cachexia↓, 1,   chemoP↑, 1,  
Total Targets: 164

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 2,   Ferroptosis↓, 1,   GPx↑, 2,   GPx4∅, 1,   GSH↑, 3,   GSTs↑, 1,   HO-1↑, 3,   HO-1∅, 1,   lipid-P↓, 3,   MDA↓, 2,   NQO1↑, 1,   NRF2↑, 2,   NRF2∅, 1,   ROS↓, 4,   SOD↑, 4,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,  

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

BAX↓, 1,   Bax:Bcl2↓, 1,   Bcl-2↑, 1,   Casp1↓, 1,   Casp3↓, 3,   Casp9↓, 1,   Casp9↑, 1,   Ferroptosis↓, 1,   iNOS↓, 1,  

Protein Folding & ER Stress ⓘ

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

DNA Damage & Repair ⓘ

p‑γH2AX↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,  

Migration ⓘ

TXNIP↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

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

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,   tau↓, 1,   TrkB↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   BACE↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   BloodF↑, 1,   GutMicro↑, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 1,   toxicity↓, 1,  
Total Targets: 78

Scientific Paper Hit Count for: HO-1, HMOX1
11 Luteolin
2 Chemotherapy
1 Baicalein
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#:597  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page