Quercetin / TGF-β 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


TGF-β, transforming growth factor-beta: Click to Expand ⟱
Source: HalifaxProj(inhibit) CGL-CS TCGA
Type:
Human malignancies frequently exhibit mutations in the TGF-β pathway, and overactivation of this system is linked to tumor growth by promoting angiogenesis and inhibiting the innate and adaptive antitumor immune responses.
Anti-inflammatory cytokine.
In normal tissues, TGF-β plays an essential role in cell cycle regulation, immune function, and tissue remodeling.
- In early carcinogenesis, TGF-β typically acts as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis.

In advanced cancers, cells frequently become resistant to the growth-inhibitory effects of TGF-β.
- TGF-β then switches roles and promotes tumor progression by stimulating epithelial-to-mesenchymal transition (EMT), cell invasion, metastasis, and immune evasion.

Non-canonical (Smad-independent) pathways, such as MAPK, PI3K/Akt, and Rho signaling, also contribute to TGF-β-mediated responses.

Elevated levels of TGF-β have been detected in many advanced-stage cancers, including breast, lung, colorectal, pancreatic, and prostate cancers.
 - The switch from a tumor-suppressive to a tumor-promoting role is often associated with increased TGF-β production and activation in the tumor microenvironment.

High TGF-β expression or signaling activity is frequently correlated with aggressive disease features, resistance to therapy, increased metastasis, and poorer overall survival in many cancer types.
Scientific Papers found: Click to Expand⟱
26- EGCG,  QC,  docx,    Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy
- vitro+vivo, Pca, PC3
BAD↓, cl‑PARP↑, Casp7↑, IκB↓, Ki-67↓, VEGF↓, EGFR↓, FGF↓, TGF-β↓, TNF-α↓, SCF↓, Bax:Bcl2↑, NF-kB↓, chemoP↑, ChemoSen↑, TumVol↓,
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↓,
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/DDIT3↑, ROS↓, LDH↑, GRP78/BiP↑, ERK↑, MDA↓, SOD↑, GSH↑, NRF2↑, VEGF↓, PDGF↓, EGF↓, FGF↓, TNF-α↓, TGF-β↓, VEGFR2/KDR/Flk1↓, EGFR↓, FGFR1↓, mTOR↓, cMyc↓, MMPs↓, LC3B-II↑, Beclin-1↑, IL1β↓, CRP↓, IL10↓, COX2/PTGS2↓, IL6↓, TLR4↓, Shh↓, HER2/EBBR2↓, NOTCH↓, DR5↑, HSP70/HSPA5↓, CSCs↓, angioG↓, MMP2↓, MMP9↓, IGFBP3↑, uPA↓, uPAR↓, RAS↓, Raf↓, TSP-1↑,
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/KDR/Flk1↓, EMT↓, EGFR↓, MMP2↓, MMP↓, TumMeta↓, MMPs↓, Akt↓, Snail↓, N-cadherin↓, Vim↓, E-cadherin↑, STAT3↓, TGF-β↓, ROS↓, P53↑, BAX↑, PKCδ↓, PI3K↓, COX2/PTGS2↓, 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↑,
103- RES,  CUR,  QC,    The effect of resveratrol, curcumin and quercetin combination on immuno-suppression of tumor microenvironment for breast tumor-bearing mice
- vitro+vivo, BC, 4T1
ROS↑, MMP↓, Bcl-2↓, BAX↑, Casp9↑, T-Cell↑, TGF-β↓,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↓, 1,   GSH↑, 1,   HO-1↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 4,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

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

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 3,   LDH↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 1,   BAD↓, 1,   Bak↑, 1,   BAX↑, 4,   Bax:Bcl2↑, 1,   Bcl-2↓, 3,   Casp10↑, 1,   Casp3↓, 2,   Casp3↑, 2,   Casp7↑, 1,   Casp8↑, 1,   Casp9↑, 4,   cFLIP↓, 1,   Cyt‑c↑, 2,   Diablo↑, 1,   DR5↑, 2,   Fas↑, 1,   FasL↑, 1,   iNOS↓, 2,   MAPK↓, 1,   MAPK↑, 1,   p38↑, 1,   survivin↓, 1,   TNFR 1↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   miR-21↑, 1,   other↓, 1,   p‑pRB↓, 1,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   HSP27↓, 1,   HSP70/HSPA5↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DFF45↑, 1,   DNMTs↓, 1,   P53↑, 3,   PARP↓, 1,   cl‑PARP↑, 2,   PARP1↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

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

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

CSCs↓, 2,   EMT↓, 3,   ERK↑, 1,   p‑ERK↓, 1,   FGF↓, 2,   GSK‐3β↓, 1,   HDAC↓, 1,   IGFBP3↑, 1,   mTOR↓, 2,   p‑mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 3,   PTEN↑, 1,   RAS↓, 1,   SCF↓, 1,   Shh↓, 1,   STAT3↓, 2,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↓, 1,   Ca+2↝, 1,   CLDN2↓, 1,   COL1↓, 1,   COL3A1↓, 1,   CXCL12↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   Ki-67↓, 2,   LEF1↓, 1,   MMP2↓, 3,   MMP7↓, 1,   MMP9↓, 2,   MMPs↓, 3,   N-cadherin↓, 1,   PDGF↓, 1,   PKCδ↓, 1,   RAGE↓, 1,   Slug↓, 1,   Snail↓, 2,   TGF-β↓, 5,   TSP-1↑, 3,   TumMeta↓, 1,   uPA↓, 2,   uPAR↓, 1,   Vim↓, 2,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 2,   EGFR↓, 4,   Hif1a↓, 1,   NO↓, 1,   VEGF↓, 4,   VEGFR2/KDR/Flk1↓, 2,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3,   CRP↓, 1,   CXCR4↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL10↓, 2,   IL1β↓, 1,   IL6↓, 3,   IL8↓, 1,   Inflam↓, 1,   IκB↓, 1,   NF-kB↓, 3,   T-Cell↑, 1,   TLR4↓, 1,   TNF-α↓, 3,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 2,   eff↑, 4,   P450↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

CRP↓, 1,   EGFR↓, 4,   HER2/EBBR2↓, 1,   IL6↓, 3,   Ki-67↓, 2,   LDH↑, 1,   RAGE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 1,   TumVol↓, 1,  
Total Targets: 150

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,  
Total Targets: 5

Scientific Paper Hit Count for: TGF-β, transforming growth factor-beta
5 Quercetin
1 EGCG (Epigallocatechin Gallate)
1 Docetaxel
1 Resveratrol
1 Curcumin
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#:304  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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