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.

-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⟱
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↓, *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↓, 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↓, 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↓, 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↓, *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↓, *NRF2↑, *HO-1↑, *IL1β↓, *IL17↓, *MCP1↓, PKCδ↓, ERK↓, BAX↓, cMyc↓, KRAS↓, ROS↓, selectivity↑, tumCV↓, Apoptosis↑, TumCCA↑, eff↑, P-gp↓, 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↓,
3108- VitC,  QC,    The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells
- in-vitro, BC, MDA-MB-231 - in-vitro, Lung, A549
NRF2↓, HO-1↓, ROS↑, NRF2⇅,

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 ⓘ

antiOx↑, 1,   Catalase↑, 1,   GSH↓, 2,   GSH↑, 1,   HO-1↓, 1,   HO-1↑, 2,   lipid-P↓, 1,   NRF2↓, 1,   NRF2↑, 1,   NRF2⇅, 1,   ROS↓, 2,   ROS↑, 3,   ROS⇅, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

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

Core Metabolism/Glycolysis ⓘ

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

Cell Death ⓘ

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 ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

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

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

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 ⓘ

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 ⓘ

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

Barriers & Transport ⓘ

P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

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

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   IL6↓, 2,   KRAS↓, 1,   RAGE↓, 1,  
Total Targets: 113

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

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

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   PGC-1α↑, 1,  

Core Metabolism/Glycolysis ⓘ

PKM2↓, 1,   PPARα↑, 1,   SIRT1↑, 3,  

Cell Death ⓘ

Akt↑, 1,   iNOS↓, 1,   MAPK↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   PI3K↑, 1,  

Migration ⓘ

AP-1↓, 1,   Ca+2↓, 1,   PKCδ↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

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

Synaptic & Neurotransmission ⓘ

AChE↓, 2,   BChE↓, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 2,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BP↓, 2,   CRP↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 4,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 3,   Pain↓, 1,  
Total Targets: 64

Scientific Paper Hit Count for: HO-1, HMOX1
10 Quercetin
1 Vitamin C (Ascorbic Acid)
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#:%
  wNotes=0  sortOrder:rid,rpid

 

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