Fisetin / MMP7 Cancer Research Results

FIS, Fisetin: Click to Expand ⟱
Features:
Fisetin is a plant based flavonoid. Found in strawberries(160ug/g), apples, persimmons, onions, cucumbers, grapes.

-Note half-life 3-4hrs
- Oral BioAv low (40-50%)
Pathways:
- induce ROS production in cancer cells, but also known to reduce it.
Also a claim Fisetin-Induced Reactive Oxygen Species Production Has No Effect on Apoptosis in RCC cells
Also one claim (NAC 10-20mM levels) that NAC enhances ROS/apoptosis
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Does not appear to lower antioxidants in cancer cells
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits HIF-1α↓, cMyc↓, LDH↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells : CD133↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Fisetin effect on Cancer Cells
Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR signaling ↔ adaptive suppression Driver Loss of survival and growth signaling Fisetin consistently suppresses pro-survival PI3K/AKT signaling, supporting growth inhibition and sensitization to stress
2 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Driver Suppression of inflammatory survival transcription NF-κB inhibition contributes to anti-inflammatory effects and reduced tumor-supportive signaling
3 Reactive oxygen species (ROS) ↑ ROS (context- & dose-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Fisetin can act as a pro-oxidant in cancer cells at higher stress/dose while remaining antioxidant in normal cells
4 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Secondary Execution of intrinsic apoptosis Mitochondrial apoptosis occurs downstream of signaling and redox disruption
5 Cell cycle regulation ↑ G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream pathway inhibition rather than direct CDK blockade
6 Senescence / senolytic action ↑ senescence clearance (senescent-like tumor/stroma subsets) ↓ senescent cell burden (selective) Secondary Selective vulnerability of senescent-like cells Fisetin is commonly described as senolytic; in cancer context this may impact tumor microenvironment and therapy-induced senescence
7 MAPK stress signaling (JNK / p38) ↑ JNK / ↑ p38 (context-dependent) ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation often follows ROS increase and supports apoptotic signaling
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 activation reflects redox buffering responses rather than primary cytotoxicity
9 Migration / invasion (EMT, MMP axis) ↓ migration & invasion Phenotypic Anti-metastatic phenotype Reduced EMT and protease activity limit invasive behavior downstream of signaling changes


MMP7, metalloproteinase-7: Click to Expand ⟱
Source:
Type:
MMP-7, or matrix metalloproteinase-7, is an enzyme that plays a significant role in the degradation of extracellular matrix components. It is part of a larger family of matrix metalloproteinases (MMPs) that are involved in various physiological and pathological processes, including tissue remodeling, wound healing, and inflammation.
MMP-7 can facilitate tumor invasion and metastasis by breaking down the extracellular matrix, allowing cancer cells to migrate and invade surrounding tissues.
Elevated levels of MMP-7 have been associated with poor prognosis in various cancers, including colorectal, breast, and lung cancers.


Scientific Papers found: Click to Expand⟱
2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
PI3K↓, Akt↓, mTOR↓, p38↓, *antiOx↑, *neuroP↑, Casp3↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, AMPK↑, ACC↑, DNAdam↑, MMP↓, eff↑, ROS↑, cl‑PARP↑, Cyt‑c↑, Diablo↑, P53↑, p65↓, Myc↓, HSP70/HSPA5↓, HSP27↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, TumCCA↑, CDK2↓, CDK4↓, cycD1/CCND1↓, cycA1/CCNA1↓, P21↑, MMP2↓, MMP9↓, TumMeta↓, MMP1↓, MMP3↓, MMP7↓, MET↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↑, uPA↓, ChemoSen↑, EMT↓, Twist↓, Zeb1↓, cFos↓, cJun↓, EGF↓, angioG↓, VEGF↓, eNOS↓, *NRF2↑, HO-1↑, NRF2↓, GSTs↓, ATF4↓,
2827- FIS,    The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
- Review, Var, NA
*antiOx↑, *Inflam↓, neuroP↑, hepatoP↑, RenoP↑, cycD1/CCND1↓, TumCCA↑, MMPs↓, VEGF↓, MAPK↓, NF-kB↓, angioG↓, Beclin-1↑, LC3s↑, ATG5↑, Bcl-2↓, BAX↑, Casp↑, TNF-α↓, Half-Life↓, MMP↓, mt-ROS↑, cl‑PARP↑, CDK2↓, CDK4↓, Cyt‑c↑, Diablo↑, DR5↑, Fas↑, PCNA↓, Ki-67↓, p‑H3↓, chemoP↑, Ca+2↑, Dose↝, CDC25↓, CDC2↓, CHK1↑, Chk2↑, ATM↑, PCK1↓, RAS↓, p‑p38↓, Rho↓, uPA↓, MMP7↓, MMP13↓, GSK‐3β↑, E-cadherin↑, survivin↓, VEGFR2↓, IAP2↓, STAT3↓, JAK1↓, mTORC1↓, mTORC2↓, NRF2↑,
2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, mtDam↑, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, Bak↑, BIM↑, Bcl-xL↓, Bcl-2↓, P53↑, ROS↑, AMPK↑, Casp9↑, Casp3↑, BID↑, AIF↑, Akt↓, mTOR↓, MAPK↓, Wnt↓, β-catenin/ZEB1↓, TumCCA↑, P21↑, p27↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, TumMeta↓, uPA↓, E-cadherin↑, Vim↓, EMT↓, Twist↓, DNAdam↑, ROS↓, COX2↓, PGE2↓, HSF1↓, cFos↓, cJun↓, AP-1↓, Mcl-1↓, NF-kB↓, IRE1↑, ER Stress↑, ATF4↑, GRP78/BiP↑, MMP2↓, MMP9↓, TCF-4↓, MMP7↓, RadioS↑, TOP1↓, TOP2↓,
2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, ROS↑, Apoptosis↑, Bcl-2↓, BAX↑, cl‑Casp9↑, cl‑Casp3↑, Cyt‑c↑, lipid-P↓, TumCG↓, TumCA↓, TumCMig↓, TumCI↓, uPA↓, ERK↓, MMP9↓, NF-kB↓, cFos↓, cJun↓, AP-1↓, TumCCA↑, AR↓, mTORC1↓, mTORC2↓, TSC2↑, EGF↓, TGF-β↓, EMT↓, P-gp↓, PI3K↓, Akt↓, mTOR↓, eff↑, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, ChemoSen↑, CDK2↓, CDK4↓, cycE/CCNE↓, cycD1/CCND1↓, P21↑, COX2↓, Wnt↓, EGFR↓, β-catenin/ZEB1↓, TCF-4↓, MMP7↓, RadioS↑, eff↑,
2843- FIS,    Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential
- Review, Var, NA
NRF2↑, Keap1↓, ChemoSen↑, BioAv↓, Cyt‑c↑, Casp3↑, Casp9↑, BAX↑, tumCV↓, Mcl-1↓, cl‑PARP↑, IGF-1↓, Akt↓, CDK6↓, TumCCA↑, P53?, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, MMP2↓, MMP9↓, MMP1↓, MMP7↓, MMP3↓, VEGF↓, PI3K↓, mTOR↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, ERK↓, ROS↑, angioG↓, TNF-α↓, PGE2↓, iNOS↓, NO↓, IL6↓, HSP70/HSPA5↝, HSP27↝,
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↓, uPA↓, PI3K↓, FAK↓, MEK↓, ERK↓, JNK↓, p38↓, cJun↓, FOXO3↑,

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

GSTs↓, 1,   HO-1↑, 1,   Keap1↓, 1,   lipid-P↓, 1,   NRF2↓, 1,   NRF2↑, 2,   ROS↓, 2,   ROS↑, 5,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics

AIF↑, 1,   CDC2↓, 1,   CDC25↓, 1,   EGF↓, 2,   MEK↓, 1,   MMP↓, 4,   mtDam↑, 1,  

Core Metabolism/Glycolysis

ACC↑, 1,   AMPK↑, 2,   PCK1↓, 1,  

Cell Death

Akt↓, 4,   Apoptosis↑, 1,   BAD↑, 1,   Bak↑, 1,   BAX↑, 4,   Bcl-2↓, 4,   Bcl-xL↓, 1,   BID↑, 1,   BIM↑, 2,   Casp↑, 2,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp9↑, 2,   cl‑Casp9↑, 1,   Chk2↑, 1,   Cyt‑c↑, 6,   Diablo↑, 3,   DR5↑, 1,   Endon↑, 1,   Fas↑, 1,   IAP2↓, 1,   iNOS↓, 2,   JNK↓, 1,   MAPK↓, 2,   Mcl-1↓, 3,   Myc↓, 1,   p27↑, 1,   p38↓, 2,   p‑p38↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction

TSC2↑, 1,  

Transcription & Epigenetics

cJun↓, 4,   p‑H3↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

ER Stress↑, 2,   GRP78/BiP↑, 2,   HSF1↓, 1,   HSP27↓, 1,   HSP27↝, 1,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↝, 1,   HSPs↓, 1,   IRE1↑, 2,  

Autophagy & Lysosomes

ATG5↑, 1,   Beclin-1↑, 1,   LC3s↑, 1,  

DNA Damage & Repair

ATM↑, 1,   CHK1↑, 1,   DNAdam↑, 3,   P53?, 1,   P53↑, 2,   cl‑PARP↑, 4,   PCNA↓, 1,  

Cell Cycle & Senescence

CDK2↓, 5,   CDK4↓, 5,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 3,   P21↑, 3,   TumCCA↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State

cFos↓, 3,   EMT↓, 3,   ERK↓, 3,   FOXO3↑, 1,   GSK‐3β↑, 1,   IGF-1↓, 1,   mTOR↓, 4,   mTORC1↓, 2,   mTORC2↓, 2,   PI3K↓, 4,   RAS↓, 2,   STAT3↓, 1,   TCF-4↓, 2,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 1,   Wnt↓, 4,  

Migration

AP-1↓, 2,   Ca+2↑, 2,   E-cadherin↑, 3,   FAK↓, 1,   Fibronectin↓, 1,   Ki-67↓, 1,   MET↓, 1,   MMP-10↓, 1,   MMP1↓, 2,   MMP13↓, 1,   MMP2↓, 4,   MMP3↓, 2,   MMP7↓, 6,   MMP9↓, 5,   MMPs↓, 1,   N-cadherin↓, 1,   Rho↓, 1,   ROCK1↑, 1,   Snail↓, 1,   TGF-β↓, 1,   TumCA↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumMeta↓, 2,   Twist↓, 2,   uPA↓, 5,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature

angioG↓, 3,   ATF4↓, 1,   ATF4↑, 2,   EGFR↓, 3,   eNOS↓, 1,   NO↓, 1,   VEGF↓, 4,   VEGFR2↓, 1,  

Barriers & Transport

P-gp↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 5,   IL6↓, 1,   JAK1↓, 1,   NF-kB↓, 6,   p65↓, 2,   PGE2↓, 2,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors

AR↓, 1,   CDK6↓, 3,  

Drug Metabolism & Resistance

BioAv↓, 1,   ChemoSen↑, 3,   Dose↝, 1,   eff↑, 3,   Half-Life↓, 1,   RadioS↑, 2,  

Clinical Biomarkers

AR↓, 1,   EGFR↓, 3,   IL6↓, 1,   Ki-67↓, 1,   Myc↓, 1,  

Functional Outcomes

chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   RenoP↑, 1,  
Total Targets: 159

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 2,   NRF2↑, 1,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Functional Outcomes

neuroP↑, 1,  
Total Targets: 4

Scientific Paper Hit Count for: MMP7, metalloproteinase-7
6 Fisetin
1 Quercetin
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#:78  Target#:202  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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