Quercetin / AR 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


AR, androgen receptor: Click to Expand ⟱
Source: HalifaxProj(suppress signaling);CGL-Driver Genes
Type: Oncogene
Androgens play an important role in the proliferation, differentiation, maintenance and function of the prostate [1]. Intriguingly, they may also be involved in the development and progression of prostate cancer. Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen.

The prognostic significance of androgen receptor expression varies widely across different cancer types. In some cancers, high AR expression is associated with poor outcomes, while in others, it may indicate a better prognosis
High expression with poor prognosis is most common.

AR is used as a clinical biomarker for prostate therapy
Scientific Papers found: Click to Expand⟱
24- EGCG,  GEN,  QC,    Targeting CWR22Rv1 prostate cancer cell proliferation and gene expression by combinations of the phytochemicals EGCG, genistein and quercetin
- in-vitro, Pca, 22Rv1
NQO1↑, P53↑, NQO2↑, chemoPv↑, TumCP↓, AR↓,
67- QC,  RES,    Overexpression of c-Jun induced by quercetin and resverol inhibits the expression and function of the androgen receptor in human prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
cJun↑, AR↓,
70- QC,    Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
PSA↓, AR↓, NKX3.1↓, HK2↓,
72- QC,  Se,    Selenium- or quercetin-induced retardation of DNA synthesis in primary prostate cells occurs in the presence of a concomitant reduction in androgen-receptor activity
- in-vitro, Pca, PECs - in-vitro, Pca, LNCaP - in-vitro, Pca, NIH-3T3
AR↓,
75- QC,  ENZ,    Quercetin targets hnRNPA1 to overcome enzalutamide resistance in prostate cancer cells
- in-vitro, Pca, HEK293 - in-vitro, NA, 22Rv1 - in-vitro, NA, C4-2B
hnRNPA1↓, PSA↓, NKX3.1↓, FKBP5↓, UBE2C↓, AR-FL↓, AR-V7↑, AR↓, eff↑, TumVol↓, BioAv↓,
79- QC,    Chemopreventive Effect of Quercetin in MNU and Testosterone Induced Prostate Cancer of Sprague-Dawley Rats
- in-vivo, Pca, NA
GSH↑, SOD↑, Catalase↑, GPx↑, GSR↑, IGF-1R↓, Akt↓, AR↓, TumCP↓, lipid-P↓, H2O2↓, Raf↓, p‑MEK↓, Bcl-2↑, Bcl-xL↑, Casp3↑, Casp8↑, Casp9↑,
81- QC,  EGCG,    Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea
- in-vivo, Pca, NA
COMT↓, MRP1↓, Ki-67↓, Bax:Bcl2↑, AR↓, Akt↓, p‑ERK↓, COMT↓, eff↑, chemoPv↑, BioAv↑,
82- QC,  ATG,    Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells
- in-vitro, Pca, LNCaP
AR↓, PI3K/Akt↓, miR-21↓, STAT3↓, BAD↓, PRAS40↓, GSK‐3β↓, PSA↓, NKX3.1↑, Bax:Bcl2↑, miR-19b↓, miR-148a↓, AMPKα↓, TumCP↓, chemoPv↑, TumCMig↓,
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↓,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 2,   GPx↑, 1,   GSH↑, 2,   GSR↑, 1,   H2O2↓, 1,   lipid-P↓, 2,   NQO1↑, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

p‑MEK↓, 1,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

HK2↓, 1,   PI3K/Akt↓, 1,  

Cell Death ⓘ

Akt↓, 3,   BAD↓, 1,   BAX↑, 1,   Bax:Bcl2↑, 2,   Bcl-2↑, 1,   Bcl-xL↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   miR-21↓, 1,  

Protein Folding & ER Stress ⓘ

NQO2↑, 1,  

DNA Damage & Repair ⓘ

NKX3.1↓, 2,   NKX3.1↑, 1,   P53↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

AR-FL↓, 1,   AR-V7↑, 1,   p‑ERK↓, 1,   GSK‐3β↓, 1,   IGF-1R↓, 2,   STAT3↓, 1,  

Migration ⓘ

hnRNPA1↓, 1,   Ki-67↓, 1,   miR-148a↓, 1,   miR-19b↓, 1,   TumCMig↓, 1,   TumCP↓, 4,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 3,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 9,   COMT↓, 2,   FKBP5↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   eff↑, 2,   MRP1↓, 1,  

Clinical Biomarkers ⓘ

AR↓, 9,   Ki-67↓, 1,   PSA↓, 3,  

Functional Outcomes ⓘ

chemoPv↑, 3,   PRAS40↓, 1,   TumVol↓, 1,   UBE2C↓, 1,  
Total Targets: 55

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   H2O2↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   ROS↓, 1,   SOD↑, 1,   SOD2↑, 1,  

Cell Death ⓘ

Akt↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↑, 1,  

Migration ⓘ

Ca+2↓, 1,  

Immune & Inflammatory Signaling ⓘ

IKKα↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  
Total Targets: 23

Scientific Paper Hit Count for: AR, androgen receptor
9 Quercetin
2 EGCG (Epigallocatechin Gallate)
1 Genistein (soy isoflavone)
1 Resveratrol
1 Selenium
1 enzalutamide
1 Arctigenin
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#:15  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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