Quercetin / MMP9 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


MMP9, MMP9: Click to Expand ⟱
Source: HalifaxProj(suppress)
Type:
Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components.
MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis).
Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
2343- QC,    Pharmacological Activity of Quercetin: An Updated Review
- Review, Nor, NA
*ROS↓, *GSH↑, *Catalase↑, *SOD↑, *MDA↓, *GPx↑, *Copper↓, *Iron↓, Apoptosis↓, TumCCA↑, MMP2↓, MMP9↓, GlucoseCon↓, lactateProd↓, PKM2↓, GLUT1↓, LDHA↓, ROS↑,
2341- QC,    Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction
- in-vitro, BC, MCF7 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
MMP2↓, MMP9↓, VEGF↓, Glycolysis↓, lactateProd↓, PKM2↓, GLUT1↓, LDHA↓, TumAuto↑, Akt↓, mTOR↓, TumMeta↓, MMP3↓, eff↓, GlucoseCon↓, lactateProd↓, TumAuto↑, LC3B-II↑,
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↓,
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↑,
3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, TumCCA↓, HSPs↓, RAS↓, ROS↑, Ca+2↑, MMP↓, Cyt‑c↑, Endon↑, MMP9↓, MMP2↓, MMP7↓, MMP-10↓, VEGF↓, NF-kB↓, p65↓, iNOS↓, COX2/PTGS2↓, uPA↓, PI3K↓, FAK↓, MEK↓, ERK↓, JNK↓, p38↓, cJun↓, FOXO3↑,
3370- QC,    Quercetin downregulates matrix metalloproteinases 2 and 9 proteins expression in prostate cancer cells (PC-3)
- in-vitro, Pca, PC3
MMP2↓, MMP9↓,
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↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

GSH↑, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 6,   SOD↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 2,   EGF↓, 1,   FGFR1↓, 1,   MEK↓, 1,   MMP↓, 4,   Raf↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

cMyc↓, 2,   GlucoseCon↓, 3,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 4,   LDH↑, 2,   LDHA↓, 2,   PKM2↓, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 3,   p‑Akt↓, 2,   Apoptosis↓, 1,   Apoptosis↑, 2,   Bak↑, 1,   BAX↑, 3,   Bcl-2↓, 2,   Casp12↑, 1,   Casp3↓, 2,   Casp3↑, 2,   Casp9↑, 3,   cFLIP↓, 1,   Cyt‑c↑, 5,   Diablo↑, 1,   DR5↑, 1,   Endon↑, 2,   FasL↑, 1,   iNOS↓, 2,   JNK↓, 1,   MAPK↓, 2,   MAPK↑, 1,   p38↓, 2,   p38↑, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↓, 1,   ac‑H3↑, 1,   ac‑H4↑, 1,   miR-21↑, 1,   p‑pRB↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 2,   ER Stress↑, 1,   GRP78/BiP↑, 2,   HSP70/HSPA5↓, 1,   HSPs↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1,   LC3B-II↑, 2,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

DNMTs↓, 1,   P53↑, 2,   PARP↓, 1,   PARP1↑, 1,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 1,   CDK2↑, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 2,   P21↓, 1,   TumCCA↓, 1,   TumCCA↑, 4,  

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

CD24↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 3,   ERK↓, 1,   ERK↑, 1,   p‑ERK↓, 2,   FGF↓, 1,   FOXO3↑, 1,   HDAC↓, 1,   IGFBP3↑, 1,   mTOR↓, 2,   p‑mTOR↓, 1,   NOTCH↓, 1,   PI3K↓, 3,   PTEN↑, 1,   RAS↓, 2,   Shh↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↓, 1,   Ca+2↑, 3,   CLDN2↓, 1,   CXCL12↓, 1,   E-cadherin↑, 1,   FAK↓, 2,   Ki-67↓, 1,   MMP-10↓, 1,   MMP2↓, 8,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 8,   MMPs↓, 3,   N-cadherin↓, 1,   PDGF↓, 1,   PKA↓, 1,   PKCδ↓, 1,   ROCK1↑, 1,   Slug↓, 1,   Snail↓, 1,   TGF-β↓, 2,   TIMP1↑, 1,   TSP-1↑, 2,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 1,   TumMeta↓, 4,   Twist↓, 2,   uPA↓, 3,   uPAR↓, 1,   Vim↓, 1,   α-SMA↓, 1,   α-SMA↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 2,   Hif1a↓, 2,   NO↓, 1,   VEGF↓, 5,   VEGFR2/KDR/Flk1↓, 2,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 2,   P-gp/ABCB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3,   CRP↓, 1,   CXCR4↓, 1,   IL10↓, 2,   IL1β↓, 1,   IL6↓, 2,   NF-kB↓, 2,   p65↓, 1,   TLR4↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 1,   ChemoSen↑, 2,   eff↓, 1,   eff↑, 4,   selectivity↑, 1,  

Clinical Biomarkers(tgid=22) ⓘ

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

Functional Outcomes(tgid=23) ⓘ

TumVol↓, 1,  
Total Targets: 155

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Catalase↑, 1,   Copper↓, 1,   GPx↑, 1,   GSH↑, 1,   Iron↓, 1,   MDA↓, 1,   ROS↓, 1,   SOD↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 3,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP↑, 2,   neuroP↑, 2,  
Total Targets: 14

Scientific Paper Hit Count for: MMP9, MMP9
8 Quercetin
1 Fisetin
1 Kaempferol
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#:203  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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