Quercetin / P-gp/ABCB1 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


P-gp/ABCB1, permeability-glycoprotein: Click to Expand ⟱
Source:
Type:
P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is a membrane protein that plays a crucial role in the transport of various substances across cellular membranes. It is part of the ATP-binding cassette (ABC) transporter family.
P-glycoprotein is often overexpressed in a variety of cancers, including breast cancer, lung cancer, leukemia, and ovarian cancer.

- The overexpression of P-glycoprotein (P-gp), is widely considered as an important reason for the MDR (multidrug resistance).

ABCB1 - ATP-Binding Cassette Subfamily B Member 1 / P-Glycoprotein

Abbreviation: ABCB1, P-gp, P-glycoprotein, MDR1

Type: ATP-dependent membrane efflux transporter / multidrug resistance protein

Function: ABCB1 encodes P-glycoprotein, an ATP-binding cassette transporter that exports a broad range of drugs, xenobiotics, lipids, and other substrates across cellular membranes. It is highly expressed in barrier tissues including the intestine, liver, kidney, placenta, and blood-brain barrier, where it limits tissue accumulation of potentially harmful compounds.

Cancer: ↑ Frequently overexpressed or functionally activated in drug-resistant tumors. Increased ABCB1 lowers intracellular concentrations of many anticancer agents by actively transporting them out of cancer cells, producing multidrug resistance and reducing chemotherapy effectiveness.

Alzheimer's Disease: ↓ Reduced ABCB1/P-glycoprotein expression or transport activity at the blood-brain barrier is associated with impaired amyloid-β clearance from the brain. Lower P-gp function correlates with increased cerebral Aβ accumulation and may contribute to Alzheimer's disease progression.
Scientific Papers found: Click to Expand⟱
5643- BCA,  GEN,  QC,  SIL,  KaempF  P-glycoprotein inhibitors of natural origin as potential tumor chemo-sensitizers: A review
- in-vitro, NA, NA
P-gp/ABCB1↓,
926- QC,  PacT,  doxoR,  Tam,    Bioenhancers from mother nature and their applicability in modern medicine
- Review, Nor, NA
*BioEnh↑, BioEnh↑, BioEnh↑, BioEnh↑, BioEnh↑, BioEnh↑, BioEnh↑, P-gp/ABCB1↓,
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↓,
96- QC,  docx,    Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways
- vitro+vivo, Pca, LNCaP - in-vitro, Pca, PC3
PI3K/Akt↓, Ki-67↓, BAX↑, Bcl-2↓, EpCAM↓, Twist↓, E-cadherin↑, P-gp/ABCB1↓, TumCP↓, TumCMig↓, TumCI↓,
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/PTGS2↓, *NRF2↑, *HO-1↑, *IL1β↓, *IL17↓, *MCP1/CCL2↓, PKCδ↓, ERK↓, BAX↓, cMyc↓, KRAS↓, ROS↓, selectivity↑, tumCV↓, Apoptosis↑, TumCCA↑, eff↑, P-gp/ABCB1↓, eff↑, eff↑, eff↑, eff↑, CycB/CCNB1↓, CDK1↓, CDK4↓, CDK2↓, TOP2↓, Cyt‑c↑, cl‑PARP↑, MMP↓, HSP70/HSPA5↓, HSP90↓, MDM2↓, RAS↓, eff↑,
3374- QC,    Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis
- Review, Oral, NA - Review, AD, NA
α-SMA↓, α-SMA↑, TumCP↓, tumCV↓, TumVol↓, TumCI↓, TumMeta↓, TumCMig↓, ROS↑, Apoptosis↑, BioAv↓, *neuroP↑, *antiOx↑, *Inflam↓, *Aβ↓, *cardioP↑, MMP↓, Cyt‑c↑, MMP2↓, MMP9↓, EMT↓, MMPs↓, Twist↓, Slug↓, Ca+2↑, AIF↑, Endon↑, P-gp/ABCB1↓, LDH↑, HK2↓, PKA↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, GRP78/BiP↑, Casp12↑, CHOP/DDIT3↑,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↓, 1,   HO-1↑, 1,   ROS↓, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 1,   MMP↓, 3,   XIAP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 2,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   LDH↑, 1,   PI3K/Akt↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Apoptosis↑, 3,   BAX↓, 1,   BAX↑, 2,   Bcl-2↓, 2,   Casp10↑, 1,   Casp12↑, 1,   Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 2,   DR5↑, 1,   Endon↑, 1,   Fas↑, 1,   iNOS↓, 1,   MDM2↓, 1,   survivin↓, 1,   TNFR 1↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

Sp1/3/4↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 1,   GRP78/BiP↑, 1,   HSP27↓, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 1,  

DNA Damage & Repair(tgid=10) ⓘ

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

Cell Cycle & Senescence(tgid=11) ⓘ

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

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

CSCs↓, 1,   EMT↓, 2,   EpCAM↓, 1,   ERK↓, 1,   GSK‐3β↓, 1,   mTOR↓, 1,   NOTCH1↓, 1,   PI3K↓, 1,   RAS↓, 1,   STAT3↓, 1,   TOP2↓, 1,  

Migration(tgid=13) ⓘ

Ca+2↑, 1,   Ca+2↝, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   KRAS↓, 1,   LEF1↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 1,   MMPs↓, 2,   PKA↓, 1,   PKCδ↓, 1,   RAGE↓, 1,   Slug↓, 2,   Snail↓, 1,   TGF-β↓, 1,   TSP-1↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 2,   Vim↓, 1,   α-SMA↓, 1,   α-SMA↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 1,   VEGF↓, 1,  

Barriers & Transport(tgid=15) ⓘ

P-gp/ABCB1↓, 6,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   BioEnh↑, 6,   eff↑, 6,   P450↓, 1,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

EGFR↓, 1,   IL6↓, 1,   Ki-67↓, 1,   KRAS↓, 1,   LDH↑, 1,   RAGE↓, 1,  

Functional Outcomes(tgid=23) ⓘ

TumVol↓, 1,  
Total Targets: 114

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Catalase↑, 1,   GSH↑, 1,   HO-1↑, 1,   Nrf1↑, 1,   NRF2↑, 2,   ROS↓, 2,   SOD↑, 1,  

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

GSK‐3β↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL10↓, 1,   IL17↓, 1,   IL1β↓, 1,   Inflam↓, 2,   MCP1/CCL2↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

tau↓, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

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

Clinical Biomarkers(tgid=22) ⓘ

BP↓, 1,  

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 2,   neuroP↑, 2,   Pain↓, 1,  
Total Targets: 26

Scientific Paper Hit Count for: P-gp/ABCB1, permeability-glycoprotein
6 Quercetin
1 Biochanin A
1 Genistein (soy isoflavone)
1 Silymarin (Milk Thistle) silibinin
1 Kaempferol
1 Paclitaxel/Taxol
1 doxorubicin
1 tamoxifen
1 Docetaxel
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#:232  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

Home Page