Quercetin / CSCs 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


CSCs, Cancer Stem Cells: Click to Expand ⟱
Source:
Type:
Cancer Stem Cells

Phytochemicals (natural plant-derived compounds) that may affect CSCs:
Curcumin
— suppresses self-renewal and pathways (Wnt/Notch/Hedgehog).
Resveratrol
— shown to reduce CSC populations and sphere formation in multiple models.
Sulforaphane (from broccoli sprouts)
— reported to inhibit CSC properties and pathways; active in vitro and in vivo.
EGCG (epigallocatechin-3-gallate, green tea)
— reduces CSC markers and sphere formation in several cancer types.
Quercetin
— reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others).
Berberine
— shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models.
Genistein (soy isoflavone)
— decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models.
Honokiol (Magnolia bark)
— shown to eliminate or suppress CSC-like populations in oral, colon, glioma models.
Luteolin
— inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models.
Withaferin A (from Withania somnifera / ashwagandha)
— multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models.

Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review
Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy
Can we utilise the circadian clock to target cancer stem cells?
Scientific Papers found: Click to Expand⟱
4687- LT,  QC,    Dietary Flavonoids Luteolin and Quercetin Suppressed Cancer Stem Cell Properties and Metastatic Potential of Isolated Prostate Cancer Cells
- in-vitro, Pca, DU145
CSCs↓, EMT↓, MMPs↓, TumCMig↓, TumCI↓,
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↓,
60- QC,  EGCG,  isoFl,    The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition
- in-vitro, Pca, pCSCs
Casp3↑, Casp7↑, Bcl-2↓, survivin↓, XIAP↓, EMT↓, Slug↓, Snail↓, β-catenin/ZEB1↓, LEF1↓, CSCs↓, Apoptosis↑, TumCMig↓, TumCI↓, CD44↓, CD133↓,
54- QC,    Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways
- in-vitro, BC, MCF-7
EMT↓, E-cadherin↑, Vim↓, MMP2↓, NOTCH1↓, PI3K/Akt↓, PI3k/Akt/mTOR↓, p‑Akt↓, EZH2↓, H3K27ac↓, TumCCA↑, CSCs↓, CDK1↓, CycB/CCNB1↓, Bcl-xL↓, Bcl-2↓, Nanog↓, H3↓,
55- QC,    Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling
- in-vitro, GC, GCSCs
Bcl-2↓, BAX↑, Cyt‑c↑, MMP↓, PI3K/Akt↓, Casp3↑, Casp9↑, TumCG↓, Apoptosis↑, CSCs↓,
58- QC,  doxoR,    Quercetin induces cell cycle arrest and apoptosis in CD133+ cancer stem cells of human colorectal HT29 cancer cell line and enhances anticancer effects of doxorubicin
- in-vitro, CRC, HT-29 - in-vitro, NA, CD133+
Bcl-2↓, TumCCA↑, CD133↓, CSCs↓, ChemoSen↑, CycB/CCNB1↑, cycE/CCNE↓, cycD1/CCND1↓, E2Fs↓,
59- QC,    Quercetin Inhibits Breast Cancer Stem Cells via Downregulation of Aldehyde Dehydrogenase 1A1 (ALDH1A1), Chemokine Receptor Type 4 (CXCR4), Mucin 1 (MUC1), and Epithelial Cell Adhesion Molecule (EpCAM)
- in-vitro, BC, MDA-MB-231
ALDH1A1↓, CXCR4↓, MUC1↓, EpCAM↓, CSCs↓, TumCP↓, TumCI↓, CD44↓, CD24↓, Apoptosis↑, TumCCA↑,
61- QC,    Midkine downregulation increases the efficacy of quercetin on prostate cancer stem cell survival and migration through PI3K/AKT and MAPK/ERK pathway
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vitro, Pca, ARPE-19
p‑PI3K↓, p‑Akt↓, p‑ERK↓, NF-kB↓, p38↓, ABCG2↓, CD44↓, CD133↓, CSCs↓,
65- QC,    Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial-mesenchymal transition and nuclear factor-κB
- in-vitro, BC, NA
HSP27↓, EMT↓, NF-kB↓, Snail↓, Vim↓, E-cadherin↑, CSCs↓,
77- QC,  EGCG,    The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition
- in-vitro, Pca, CD44+ - in-vitro, NA, CD133+ - in-vitro, NA, PC3 - in-vitro, NA, LNCaP
Casp3↑, Casp7↑, Bcl-2↓, survivin↓, XIAP↓, EMT↓, Vim↓, Slug↓, Snail↓, β-catenin/ZEB1↓, LEF1↓, TCF↓, eff↑, CSCs↓, TumCG↓, tumCV↓,
4665- QC,  Ash,  Api,    Targeting cancer stem cells by nutraceuticals for cancer therapy
- Review, Var, NA
CSCs↓,
4686- QC,    Quercetin suppresses endometrial cancer stem cells via ERα-mediated inhibition of STAT3 signaling
- in-vitro, EC, EMN8 - in-vitro, EC, EMN21
CSCs↓, ALDH1A1↓, cMyc↓, Nanog↓, OCT4↓, STAT3↓, JAK2↓, STAT3↓, eff↑,
3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
FAK↓, TumCCA↑, p‑pRB↓, CDK2↑, CycB/CCNB1↓, CDK1↓, EMT↓, PI3K↓, MAPK↓, Wnt↓, ROS↑, miR-21↑, Akt↓, NF-kB↓, FasL↑, Bak↑, BAX↑, Bcl-2↓, Casp3↓, Casp9↑, P53↑, p38↑, MAPK↑, Cyt‑c↑, PARP↓, CHOP↑, ROS↓, LDH↑, GRP78/BiP↑, ERK↑, MDA↓, SOD↑, GSH↑, NRF2↑, VEGF↓, PDGF↓, EGF↓, FGF↓, TNF-α↓, TGF-β↓, VEGFR2↓, EGFR↓, FGFR1↓, mTOR↓, cMyc↓, MMPs↓, LC3B-II↑, Beclin-1↑, IL1β↓, CRP↓, IL10↓, COX2↓, IL6↓, TLR4↓, Shh↓, HER2/EBBR2↓, NOTCH↓, DR5↑, HSP70/HSPA5↓, CSCs↓, angioG↓, MMP2↓, MMP9↓, IGFBP3↑, uPA↓, uPAR↓, RAS↓, Raf↓, TSP-1↑,
105- RES,  QC,    The Effect of Resveratrol and Quercetin on Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem Cell
- in-vitro, Pca, PANC1
N-cadherin↓, TNF-α↓, ACTA2↓, EMT↓, CD133↓, CSCs↓,

Showing Research Papers: 1 to 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   GSH↑, 1,   HO-1↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 2,   SOD↑, 1,  

Mitochondria & Bioenergetics ⓘ

EGF↓, 1,   FGFR1↓, 1,   MMP↓, 2,   Raf↓, 1,   XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,   LDH↑, 1,   PI3K/Akt↓, 2,   PI3k/Akt/mTOR↓, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 2,   Apoptosis↑, 4,   Bak↑, 1,   BAX↑, 3,   Bcl-2↓, 7,   Bcl-xL↓, 1,   Casp10↑, 1,   Casp3↓, 1,   Casp3↑, 4,   Casp7↑, 2,   Casp8↑, 1,   Casp9↑, 3,   Cyt‑c↑, 2,   DR5↑, 2,   Fas↑, 1,   FasL↑, 1,   iNOS↓, 1,   MAPK↓, 1,   MAPK↑, 1,   p38↓, 1,   p38↑, 1,   survivin↓, 3,   TNFR 1↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   H3↓, 1,   miR-21↑, 1,   other↓, 1,   p‑pRB↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   GRP78/BiP↑, 1,   HSP27↓, 2,   HSP70/HSPA5↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,  

DNA Damage & Repair ⓘ

DFF45↑, 1,   P53↑, 2,   PARP↓, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↑, 1,   CycB/CCNB1↓, 2,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   E2Fs↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 2,   CD133↓, 4,   CD24↓, 1,   CD44↓, 3,   CSCs↓, 14,   EMT↓, 8,   EpCAM↓, 1,   ERK↑, 1,   p‑ERK↓, 1,   FGF↓, 1,   GSK‐3β↓, 1,   H3K27ac↓, 1,   IGFBP3↑, 1,   mTOR↓, 2,   Nanog↓, 2,   NOTCH↓, 1,   NOTCH1↓, 2,   OCT4↓, 1,   PI3K↓, 2,   p‑PI3K↓, 1,   RAS↓, 1,   Shh↓, 1,   STAT3↓, 3,   TCF↓, 1,   TumCG↓, 2,   Wnt↓, 1,  

Migration ⓘ

ACTA2↓, 1,   Ca+2↝, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   LEF1↓, 3,   MMP2↓, 3,   MMP7↓, 1,   MMP9↓, 1,   MMPs↓, 3,   MUC1↓, 1,   N-cadherin↓, 1,   PDGF↓, 1,   RAGE↓, 1,   Slug↓, 3,   Snail↓, 4,   TGF-β↓, 2,   TSP-1↑, 2,   TumCI↓, 3,   TumCMig↓, 2,   TumCP↓, 1,   uPA↓, 1,   uPAR↓, 1,   Vim↓, 4,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

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

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 2,   IL8↓, 1,   Inflam↓, 1,   JAK2↓, 1,   NF-kB↓, 4,   TLR4↓, 1,   TNF-α↓, 3,  

Drug Metabolism & Resistance ⓘ

ABCG2↓, 1,   ChemoSen↑, 1,   eff↑, 2,   P450↓, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 2,   EZH2↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 2,   LDH↑, 1,   RAGE↓, 1,  
Total Targets: 151

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

NRF2↑, 1,   ROS↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: CSCs, Cancer Stem Cells
14 Quercetin
2 EGCG (Epigallocatechin Gallate)
1 Luteolin
1 isoflavones
1 doxorubicin
1 Ashwagandha(Withaferin A)
1 Apigenin (mainly Parsley)
1 Resveratrol
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#:795  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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