Quercetin / NO 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">Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, NOTCH">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


NO, Nitric Oxide: Click to Expand ⟱
Source:
Type:
Once the cancer has begun, NO seems to play a protumoral role rather than antitumoral one as the concentration required to cause tumor cell cytotoxicity cannot be achieved by cancer cells.
The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment.
Nitric oxide is generated by three main nitric oxide synthase isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS).

– In many cancers, especially under inflammatory conditions, iNOS expression is upregulated. In contrast, eNOS levels may also be altered in cancers such as breast or prostate cancer.

• Expression Patterns in Tumors:
– Elevated iNOS expression is commonly observed in various tumor types (e.g., colon, breast, lung, and melanoma) and is often associated with an inflammatory microenvironment.

– Changes in eNOS and nNOS expression have also been reported and may contribute to angiogenesis and tumor blood flow regulation.
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↓,
3380- QC,    Quercetin as a JAK–STAT inhibitor: a potential role in solid tumors and neurodegenerative diseases
- Review, Var, NA - Review, Park, NA - Review, AD, NA
JAK↓, STAT↓, Inflam↓, NO↓, COX2↓, CRP↓, selectivity↑, *neuroP↑, STAT3↓, cycD1/CCND1↓, MMP2↓, STAT4↓, JAK2↓, TumCP↓, Diff↓, *eff↑, *IL6↓, *TNF-α↓, *IL1β↓, *Aβ↓,
3368- QC,    The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update
- Review, Var, NA
*Inflam↓, *antiOx↑, *AntiCan↑, Casp3↓, p‑Akt↓, p‑mTOR↓, p‑ERK↓, β-catenin/ZEB1↓, Hif1a↓, AntiAg↓, VEGFR2↓, EMT↓, EGFR↓, MMP2↓, MMP↓, TumMeta↓, MMPs↓, Akt↓, Snail↓, N-cadherin↓, Vim↓, E-cadherin↑, STAT3↓, TGF-β↓, ROS↓, P53↑, BAX↑, PKCδ↓, PI3K↓, COX2↓, cFLIP↓, cycD1/CCND1↓, cMyc↓, IL6↓, IL10↓, Cyt‑c↑, TumCCA↑, DNMTs↓, HDAC↓, ac‑H3↑, ac‑H4↑, Diablo↑, Casp3↑, Casp9↑, PARP1↑, eff↑, PTEN↑, VEGF↓, NO↓, iNOS↓, ChemoSen↑, eff↑, eff↑, eff↑, uPA↓, CXCR4↓, CXCL12↓, CLDN2↓, CDK6↓, MMP9↓, TSP-1↑, Ki-67↓, PCNA↓, ROS↑, ER Stress↑,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   BAX↑, 1,   Casp3↓, 1,   Casp3↑, 1,   Casp9↑, 1,   cFLIP↓, 1,   Cyt‑c↑, 1,   Diablo↑, 1,   iNOS↓, 1,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 1,  

DNA Damage & Repair ⓘ

DNMTs↓, 1,   P53↑, 1,   PARP1↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

Diff↓, 1,   EMT↓, 1,   p‑ERK↓, 1,   HDAC↓, 1,   p‑mTOR↓, 1,   PI3K↓, 1,   PTEN↑, 1,   STAT↓, 1,   STAT3↓, 2,   STAT4↓, 1,  

Migration ⓘ

AntiAg↓, 1,   CLDN2↓, 1,   CXCL12↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   PKCδ↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TSP-1↑, 1,   TumCP↓, 1,   TumMeta↓, 1,   uPA↓, 1,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 1,   NO↓, 2,   VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 1,   CXCR4↓, 1,   IL10↓, 1,   IL6↓, 1,   Inflam↓, 1,   JAK↓, 1,   JAK2↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 4,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 1,   IL6↓, 1,   Ki-67↓, 1,  
Total Targets: 72

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   HO-1↑, 1,   MDA↓, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

PKM2↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

iNOS↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   HMGB1↓, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 2,   NF-kB↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   neuroP↑, 1,  
Total Targets: 21

Scientific Paper Hit Count for: NO, Nitric Oxide
3 Quercetin
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#:563  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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