Quercetin / MAPK 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


MAPK, mitogen-activated protein kinase: Click to Expand ⟱
Source: CGL-CS
Type:
Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death).

MAPK Pathways: The MAPK family includes several pathways, the most notable being:
1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival.
2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis.
3.p38 MAPK: Associated with inflammatory responses and apoptosis.

Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations.
Altered Expression Levels:
Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival.
Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling.
The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers.

Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.
Scientific Papers found: Click to Expand⟱
910- QC,    The Anti-Cancer Effect of Quercetin: Molecular Implications in Cancer Metabolism
tumCV↓, Apoptosis↑, PI3k/Akt/mTOR↓, Wnt/(β-catenin)↓, MAPK↝, ERK↝, TumCCA↑, H2O2↑, ROS↑, TumAuto↑, MMPs↓, P53↑, Casp3↑, Hif1a↓, cFLIP↓, IL6↓, IL10↓, lactateProd↓, Glycolysis↓, PKM2↓, GLUT1↓, COX2↓, VEGF↓, OCR↓, ECAR↓, STAT3↓, MMP2↓, MMP9:TIMP1↓, mTOR↓,
3338- QC,    Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy
- Review, Var, NA - Review, Stroke, NA
*antiOx↑, *GSH↑, *ROS↓, *Dose↑, *NADPH↓, *AMP↓, *NF-kB↓, *p38↑, *MAPK↑, *SOD↑, *MDA↓, *iNOS↓, *Catalase↑, *PI3K↑, *Akt↑, *lipid-P↓, *memory↑, *radioP↑, *neuroP↑, *MDA↓,
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↑,
39- QC,    A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells
- Analysis, NA, NA
ROS↑, GSH↓, IL6↓, COX2↓, IL8↓, iNOS↓, TNF-α↓, MAPK↑, ERK↑, SOD↑, ATP↓, Casp↑, PI3K/Akt↓, mTOR↓, NOTCH1↓, Bcl-2↓, BAX↑, IFN-γ↓, TumCP↓, TumCCA↑, Akt↓, P70S6K↓, *Keap1↓, *GPx↑, *Catalase↑, *HO-1↑, *NRF2↑, NRF2↑, eff↑, HIF-1↓,
87- QC,    Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145 - in-vitro, Pca, PC3
ROS⇅, BAX↑, PUMA⇅, β-catenin/ZEB1↓, Shc↓, TAp63α↑, MAPK↑, p‑p42↑, p‑p44↑, BIM↑,
85- QC,    Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3)
- in-vitro, Pca, PC3
uPA↓, uPAR↓, EGFR↓, NRAS↓, Jun↓, NF-kB↓, β-catenin/ZEB1↓, p38↑, MAPK↑, cJun↓, cFos↓, Raf↓, TumCI↓, TumCMig↓,
3608- QC,    Chronic diseases, inflammation, and spices: how are they linked?
- Review, Var, NA
AntiCan↑, *Inflam↓, *antiOx↑, *NF-kB↓, *MAPK↓, *PI3K↑, *Akt↑, *NRF2↑,
3603- QC,    Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus
- Review, AD, NA - Review, Diabetic, NA
*MAPK↓, *neuroP↑, *ROS↓, *Akt↓, *PI3K↓, *IL6↓, *TNF-α↓, *VEGF↓, *EGFR↓, *Casp3↓, *Bcl-2↓, *IL1β↓,
4787- QC,    Quercetin: A Phytochemical with Pro-Apoptotic Effects in Colon Cancer Cells
- Review, CRC, NA
Inflam↓, AntiCan↑, Apoptosis↑, MMP↓, P53↑, BAX↑, Casp3↑, Casp9↑, Bcl-2↓, NF-kB↓, IL6↓, IL1β↓, *antiOx↑, *lipid-P↓, *ROS↓, MAPK↓, JAK↓, STAT↓, PI3K↓, Akt↓, chemoP↑, ROS⇅, DNAdam↑, ChemoSen↝,
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↓,
3347- QC,    Recent Advances in Potential Health Benefits of Quercetin
- Review, Var, NA - Review, AD, NA
*antiOx↑, *ROS↓, *Inflam↓, TumCP↓, Apoptosis↑, *cardioP↑, *BP↓, TumMeta↓, MDR1↓, NADPH↓, ChemoSen↑, MMPs↓, TIMP2↑, *NLRP3↓, *IFN-γ↑, *COX2↓, *NF-kB↓, *MAPK↓, *CRP↓, *IL6↓, *TNF-α↓, *IL1β↓, *TLR4↑, *PKCδ↓, *AP-1↓, *ICAM-1↓, *NRF2↑, *HO-1↑, *lipid-P↓, *neuroP↑, *eff↑, *memory↑, *cognitive↑, *AChE↓, *BioAv↑, *BioAv↑, *BioAv↑, *BioAv↑, *BioAv↑,
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↑,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   GSH↑, 1,   H2O2↑, 1,   MDA↓, 1,   NRF2↑, 2,   ROS↓, 1,   ROS↑, 5,   ROS⇅, 3,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 1,   EGF↓, 2,   FGFR1↓, 1,   MMP↓, 2,   OCR↓, 1,   p‑p42↑, 1,   Raf↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   ECAR↓, 1,   Glycolysis↓, 1,   lactateProd↓, 1,   LDH↑, 1,   NADPH↓, 1,   PI3K/Akt↓, 1,   PI3k/Akt/mTOR↓, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 4,   Bak↑, 1,   BAX↑, 5,   Bcl-2↓, 4,   BIM↑, 1,   Casp↑, 1,   Casp3↓, 1,   Casp3↑, 4,   Casp9↑, 4,   cFLIP↓, 1,   Cyt‑c↑, 2,   DR5↑, 2,   FasL↑, 1,   iNOS↓, 1,   MAPK↓, 4,   MAPK↑, 4,   MAPK↝, 1,   p38↓, 1,   p38↑, 2,   PUMA⇅, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   miR-21↓, 1,   miR-21↑, 1,   p‑pRB↓, 1,   Shc↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

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

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↑, 4,   PARP↓, 1,   PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↑, 1,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 1,   P21↓, 1,   P21↑, 1,   TAp63α↑, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

CD24↓, 1,   CD44↓, 1,   cFos↓, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↑, 2,   ERK↝, 1,   p‑ERK↓, 1,   FGF↓, 1,   IGFBP3↑, 1,   Jun↓, 1,   mTOR↓, 4,   NOTCH↓, 1,   NOTCH1↓, 1,   NRAS↓, 1,   P70S6K↓, 1,   PI3K↓, 3,   RAS↓, 1,   Shh↓, 2,   STAT↓, 1,   STAT3↓, 1,   Wnt↓, 1,   Wnt/(β-catenin)↓, 2,  

Migration ⓘ

Ca+2↑, 1,   FAK↓, 1,   MMP2↓, 3,   MMP9↓, 2,   MMP9:TIMP1↓, 1,   MMPs↓, 4,   p‑p44↑, 1,   PDGF↓, 2,   TGF-β↓, 1,   TIMP1↑, 1,   TIMP2↑, 1,   TSP-1↑, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 3,   TumMeta↓, 2,   Twist↓, 1,   uPA↓, 2,   uPAR↓, 2,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 3,   HIF-1↓, 1,   Hif1a↓, 2,   VEGF↓, 4,   VEGFR2↓, 2,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

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

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   ChemoSen↝, 1,   eff↑, 1,   MDR1↓, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 3,   HER2/EBBR2↓, 1,   IL6↓, 4,   LDH↑, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   chemoP↑, 1,  
Total Targets: 149

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 1,   HO-1↑, 2,   Keap1↓, 1,   lipid-P↓, 3,   MDA↓, 2,   NRF2↑, 3,   ROS↓, 4,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMP↓, 1,   NADPH↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Akt↑, 2,   Bcl-2↓, 1,   Casp3↓, 1,   iNOS↓, 1,   MAPK↓, 3,   MAPK↑, 1,   p38↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,   PI3K↑, 2,  

Migration ⓘ

AP-1↓, 1,   PKCδ↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   ICAM-1↓, 1,   IFN-γ↑, 1,   IL1β↓, 2,   IL6↓, 2,   Inflam↓, 3,   NF-kB↓, 3,   TLR4↑, 1,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 5,   Dose↑, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,   CRP↓, 1,   EGFR↓, 1,   IL6↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 1,   memory↑, 2,   neuroP↑, 4,   radioP↑, 1,  
Total Targets: 51

Scientific Paper Hit Count for: MAPK, mitogen-activated protein kinase
12 Quercetin
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#:181  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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