Quercetin / selectivity 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


selectivity, selectivity: Click to Expand ⟱
Source:
Type:
The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues.

Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance

Factors that affect selectivity:
1. Ability of Cancer cells to preferentially absorb a product/drug
-EPR-enhanced permeability and retention of cancer cells
-nanoparticle formations/carriers may target cancer cells over normal cells
-Liposomal formations. Also negatively/positively charged affects absorbtion

2. Product/drug effect may be different for normal vs cancer cells
- hypoxia
- transition metal content levels (iron/copper) change probability of fenton reaction.
- pH levels
- antiOxidant levels and defense levels

3. Bio-availability
Scientific Papers found: Click to Expand⟱
2303- QC,  doxoR,    Quercetin greatly improved therapeutic index of doxorubicin against 4T1 breast cancer by its opposing effects on HIF-1α in tumor and normal cells
- in-vitro, BC, 4T1 - in-vivo, NA, NA
cardioP↑, hepatoP↑, TumCG↓, OS↑, ChemoSen↑, chemoP↑, Hif1a↓, *Hif1a↑, selectivity↑, TumVol↓, OS↑,
66- QC,    Emerging impact of quercetin in the treatment of prostate cancer
- Review, Pca, NA
CycB/CCNB1↓, CDK1↓, EMT↓, PI3K↓, MAPK↓, Wnt/(β-catenin)↓, PSA↓, VEGF↓, PARP↑, Casp3↑, Casp9↑, DR5↑, ROS⇅, Shh↓, P53↑, P21↑, EGFR↓, TumCCA↑, ROS↑, miR-21↓, TumCP↓, selectivity↑, PDGF↓, EGF↓, TNF-α↓, VEGFR2↓, mTOR↓, cMyc↓, MMPs↓, GRP78/BiP↑, CHOP↑,
71- QC,    Role of Bax in quercetin-induced apoptosis in human prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, PrEC - in-vitro, Pca, YPEN-1 - in-vitro, Pca, HCT116
Casp8↑, Casp9↑, PARP↑, BAD↓, BAX↑, PI3K/Akt↓, Cyt‑c↑, selectivity↑,
73- QC,    The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Pca, PC3
HSP90↓, Casp3↑, Casp9↑, TumCG↓, TumCD↑, selectivity↑, toxicity↓,
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↓,
3353- QC,    Quercetin triggers cell apoptosis-associated ROS-mediated cell death and induces S and G2/M-phase cell cycle arrest in KON oral cancer cells
- in-vitro, Oral, KON - in-vitro, Nor, MRC-5
tumCV↓, selectivity↑, TumCCA↑, TumCMig↓, TumCI↓, Apoptosis↑, TumMeta↓, Bcl-2↓, BAX↑, TIMP1↑, MMP2↓, MMP9↓, *Inflam↓, *neuroP↑, *cardioP↑, p38↓, MAPK↓, Twist↓, P21↓, cycD1/CCND1↓, Casp3↑, Casp9↑, p‑Akt↓, p‑ERK↓, CD44↓, CD24↓, ChemoSen↑, MMP↓, Cyt‑c↑, AIF↑, ROS↑, Ca+2↑, Hif1a↓, VEGF↓,
3344- QC,    Quercetin induced ROS production triggers mitochondrial cell death of human embryonic stem cells
- in-vitro, Nor, hESC
mt-ROS↑, selectivity↑, P53↑, ROS⇅,
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↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,   ROS↑, 2,   ROS⇅, 2,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   EGF↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   PI3K/Akt↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   Apoptosis↑, 2,   BAD↓, 1,   BAX↓, 1,   BAX↑, 2,   Bcl-2↓, 1,   Casp3↑, 3,   Casp8↑, 1,   Casp9↑, 4,   Cyt‑c↑, 3,   DR5↑, 1,   MAPK↓, 2,   MDM2↓, 1,   p38↓, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

miR-21↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 2,  

DNA Damage & Repair ⓘ

P53↑, 2,   PARP↑, 2,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 1,   CDK4↓, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 2,   P21↓, 1,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   CD44↓, 1,   Diff↓, 1,   EMT↓, 1,   ERK↓, 1,   p‑ERK↓, 1,   mTOR↓, 1,   PI3K↓, 1,   RAS↓, 1,   Shh↓, 1,   STAT↓, 1,   STAT3↓, 1,   STAT4↓, 1,   TOP2↓, 1,   TumCG↓, 2,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

Ca+2↑, 1,   KRAS↓, 1,   MMP2↓, 2,   MMP9↓, 1,   MMPs↓, 1,   PDGF↓, 1,   PKCδ↓, 1,   TIMP1↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 1,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   Inflam↓, 1,   JAK↓, 1,   JAK2↓, 1,   PSA↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   eff↑, 6,   selectivity↑, 8,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 1,   KRAS↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   OS↑, 2,   toxicity↓, 1,   TumVol↓, 1,  
Total Targets: 96

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GSH↑, 1,   HO-1↑, 1,   Nrf1↑, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 2,   IL6↓, 1,   Inflam↓, 2,   MCP1↓, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

BP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   neuroP↑, 3,   Pain↓, 1,  
Total Targets: 29

Scientific Paper Hit Count for: selectivity, selectivity
8 Quercetin
1 doxorubicin
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#:1110  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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