Quercetin / HO-1 Cancer Research Results

QC, Quercetin: Click to Expand ⟱
Features:
Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.
EMIQ bioavialability is about 3X that of Quercetin (Example Natural Factors brand)
Isoquercitrin is high bioaviability and efficiacy but at this time does not seem available as supplement.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose-, metal-, context-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction is a central apoptosis route in cancer cells
3 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Driver Growth and survival inhibition AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Reduced survival and inflammatory transcription NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5 MAPK signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation supports apoptosis downstream of redox stress
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects disruption of growth signaling
7 HIF-1α hypoxia signaling ↓ HIF-1α ↔ minimal Secondary Reduced hypoxia tolerance Quercetin interferes with hypoxia-driven transcriptional programs
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 induction reflects redox buffering rather than primary cytotoxicity


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⟱
7835- ISQ,  QC,    Synergistic Protection by Isoquercitrin and Quercetin against Glutamate-Induced Oxidative Cell Death in HT22 Cells via Activating Nrf2 and HO-1 Signaling Pathway: Neuroprotective Principles and Mechanisms of Dendropanax morbifera Leaves
- in-vitro, AD, HT22
*Apoptosis↓, *ROS↓, *SOD2↑, *Ca+2↓, *mtDam↓, *NRF2↑, *HO-1↑, *other↑, *AIF↓, *LC3‑Ⅱ/LC3‑Ⅰ↓, *eff↑,
2338- QC,    Quercetin: A Flavonoid with Potential for Treating Acute Lung Injury
- Review, Nor, NA
*SIRT1↑, *NLRP3↓, *Inflam↓, *TNF-α↓, *IL1β↓, *IL6↓, *PKM2↓, *HO-1↑, *ROS↓, *NO↓, *MDA↓, *antiOx↑, *COX2/PTGS2↓, *HMGB1↓, *iNOS↓, *NF-kB↓,
923- QC,    Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
- Review, Var, NA
ROS↑, GSH↓, Ca+2↝, MMP↓, Casp3↑, Casp8↑, Casp9↑, other↓, *ROS↓, *NRF2↑, HO-1↑, TumCCA↑, Inflam↓, STAT3↓, DR5↑, P450↓, MMPs↓, IFN-γ↓, IL6↓, COX2/PTGS2↓, IL8↓, iNOS↓, TNF-α↓, cl‑PARP↑, Apoptosis↑, P53↑, Sp1/3/4↓, survivin↓, TRAILR↑, Casp10↑, DFF45↑, TNFR 1↑, Fas↑, NF-kB↓, IKKα↓, cycD1/CCND1↓, Bcl-2↓, BAX↑, PI3K↓, Akt↓, E-cadherin↓, Vim↓, β-catenin/ZEB1↓, cMyc↓, EMT↓, MMP2↓, NOTCH1↓, MMP7↓, angioG↓, TSP-1↑, CSCs↓, XIAP↓, Snail↓, Slug↓, LEF1↓, P-gp/ABCB1↓, EGFR↓, GSK‐3β↓, mTOR↓, RAGE↓, HSP27↓, VEGF↓, TGF-β↓, COL1↓, COL3A1↓,
39- QC,    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells
- Analysis, NA, NA
ROS↑, GSH↓, IL6↓, COX2/PTGS2↓, IL8↓, iNOS↓, TNF-α↓, MAPK↑, ERK↑, SOD↑, ATP↓, Casp↑, PI3K/Akt↓, mTOR↓, NOTCH1↓, Bcl-2↓, BAX↑, IFN-γ↓, TumCP↓, TumCCA↑, Akt↓, P70S6K↓, *Keap1↓, *GPx↑, *Catalase↑, *HO-1↑, *NRF2↑, NRF2↑, eff↑, HIF-1↓,
5025- QC,    New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation
- Review, Nor, NA
*antiOx↑, *Inflam↓, *NRF2↓, *ROS↓, *cardioP↑, *HO-1↑, *Catalase↑, *GPx↑, *NQO1↑, *SIRT1↑,
3350- QC,    Quercetin and the mitochondria: A mechanistic view
- Review, NA, NA
*antiOx↑, *Inflam↓, *NRF2↑, ROS⇅, *NRF2↑, *HO-1↑, *PPARα↑, *PGC-1α↑, *SIRT1↑, *ATP↑, ATP↓, ERK↓, cl‑PARP↑, Casp9↑, Casp8↑, BAX↑, MMP↓, Cyt‑c↑, Casp3↑, HSP27↓, HSP72↓, RAS↓, Raf↓,
3347- QC,    Recent Advances in Potential Health Benefits of Quercetin
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *Inflam↓, TumCP↓, Apoptosis↑, *cardioP↑, *BP↓, TumMeta↓, MDR1↓, NADPH↓, ChemoSen↑, MMPs↓, TIMP2↑, *NLRP3↓, *IFN-γ↑, *COX2/PTGS2↓, *NF-kB↓, *MAPK↓, *CRP↓, *IL6↓, *TNF-α↓, *IL1β↓, *TLR4↑, *PKCδ↓, *AP-1↓, *ICAM-1↓, *NRF2↑, *HO-1↑, *lipid-P↓, *neuroP↑, *eff↑, *memory↑, *cognitive↑, *AChE↓, *BioAv↑, *BioAv↑, *BioAv↑, *BioAv↑, *BioAv↑,
3346- QC,    Regulation of the Intracellular ROS Level Is Critical for the Antiproliferative Effect of Quercetin in the Hepatocellular Carcinoma Cell Line HepG2
- in-vitro, Liver, HepG2 - in-vitro, Liver, HUH7
TumCCA↑, Apoptosis↑, P53↑, TumCP↓, ROS↓, antiOx↑, HO-1↑, CDK1↓,
3343- QC,    Quercetin, a Flavonoid with Great Pharmacological Capacity
- Review, Var, NA - Review, AD, NA - Review, Arthritis, NA
*antiOx↑, *ROS↓, *angioG↓, *Inflam↓, *BioAv↓, *Half-Life↑, *GSH↑, *SOD↑, *Catalase↑, *Nrf1↑, *BP↓, *cardioP↑, *IL10↓, *TNF-α↓, *Aβ↓, *GSK‐3β↓, *tau↓, *neuroP↑, *Pain↓, *COX2/PTGS2↓, *NRF2↑, *HO-1↑, *IL1β↓, *IL17↓, *MCP1/CCL2↓, PKCδ↓, ERK↓, BAX↓, cMyc↓, KRAS↓, ROS↓, selectivity↑, tumCV↓, Apoptosis↑, TumCCA↑, eff↑, P-gp/ABCB1↓, eff↑, eff↑, eff↑, eff↑, CycB/CCNB1↓, CDK1↓, CDK4↓, CDK2↓, TOP2↓, Cyt‑c↑, cl‑PARP↑, MMP↓, HSP70/HSPA5↓, HSP90↓, MDM2↓, RAS↓, eff↑,
3341- QC,    Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application
- Review, Var, NA - Review, Stroke, NA
*antiOx↑, *BioAv↑, *GSH↑, *AChE↓, *BChE↓, *H2O2↓, *lipid-P↓, *SOD↑, *SOD2↑, *Catalase↑, *GPx↑, *neuroP↑, *HO-1↑, *cardioP↑, *MDA↓, *NF-kB↓, *IKKα↓, *ROS↓, *PI3K↑, *Akt↑, *hepatoP↑, P53↑, BAX↑, IGF-1R↓, Akt↓, AR↓, TumCP↓, GSH↑, SOD↑, Catalase↑, lipid-P↓, *TNF-α↓, *Ca+2↓,

Showing Research Papers: 1 to 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   Catalase↑, 1,   GSH↓, 2,   GSH↑, 1,   HO-1↑, 2,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 2,   ROS⇅, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 2,   MMP↓, 3,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 2,   NADPH↓, 1,   PI3K/Akt↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   Apoptosis↑, 4,   BAX↓, 1,   BAX↑, 4,   Bcl-2↓, 2,   Casp↑, 1,   Casp10↑, 1,   Casp3↑, 2,   Casp8↑, 2,   Casp9↑, 2,   Cyt‑c↑, 2,   DR5↑, 1,   Fas↑, 1,   iNOS↓, 2,   MAPK↑, 1,   MDM2↓, 1,   survivin↓, 1,   TNFR 1↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

HSP27↓, 2,   HSP70/HSPA5↓, 1,   HSP72↓, 1,   HSP90↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DFF45↑, 1,   P53↑, 3,   cl‑PARP↑, 3,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 2,   CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 1,   EMT↓, 1,   ERK↓, 2,   ERK↑, 1,   GSK‐3β↓, 1,   IGF-1R↓, 1,   mTOR↓, 2,   NOTCH1↓, 2,   P70S6K↓, 1,   PI3K↓, 1,   RAS↓, 2,   STAT3↓, 1,   TOP2↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↝, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 1,   KRAS↓, 1,   LEF1↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMPs↓, 2,   PKCδ↓, 1,   RAGE↓, 1,   Slug↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TIMP2↑, 1,   TSP-1↑, 1,   TumCP↓, 4,   TumMeta↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 1,   HIF-1↓, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 2,   IFN-γ↓, 2,   IKKα↓, 1,   IL6↓, 2,   IL8↓, 2,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   eff↑, 7,   MDR1↓, 1,   P450↓, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

AR↓, 1,   EGFR↓, 1,   IL6↓, 2,   KRAS↓, 1,   RAGE↓, 1,  
Total Targets: 110

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 6,   Catalase↑, 4,   GPx↑, 3,   GSH↑, 2,   H2O2↓, 1,   HO-1↑, 8,   Keap1↓, 1,   lipid-P↓, 2,   MDA↓, 2,   NQO1↑, 1,   Nrf1↑, 1,   NRF2↓, 1,   NRF2↑, 7,   ROS↓, 7,   SOD↑, 2,   SOD2↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↓, 1,   ATP↑, 1,   mtDam↓, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

PKM2↓, 1,   PPARα↑, 1,   SIRT1↑, 3,  

Cell Death(tgid=5) ⓘ

Akt↑, 1,   Apoptosis↓, 1,   iNOS↓, 1,   MAPK↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

LC3‑Ⅱ/LC3‑Ⅰ↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

GSK‐3β↓, 1,   PI3K↑, 1,  

Migration(tgid=13) ⓘ

AP-1↓, 1,   Ca+2↓, 2,   PKCδ↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   NO↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3,   CRP↓, 1,   HMGB1↓, 1,   ICAM-1↓, 1,   IFN-γ↑, 1,   IKKα↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 3,   IL6↓, 2,   Inflam↓, 5,   MCP1/CCL2↓, 1,   NF-kB↓, 3,   TLR4↑, 1,   TNF-α↓, 4,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2,   BChE↓, 1,   tau↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,   NLRP3↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioAv↑, 6,   eff↑, 2,   Half-Life↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

BP↓, 2,   CRP↓, 1,   IL6↓, 2,  

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 4,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 3,   Pain↓, 1,  
Total Targets: 69

Scientific Paper Hit Count for: HO-1, HMOX1
10 Quercetin
1 isoquercitrin
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#:140  Target#:597  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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